Comparison of Adjuvant Chemotherapy Regimens in Treating Stage II/III Rectal Cancer
Study Details
Study Description
Brief Summary
This randomized phase III trial is comparing the effectiveness of three adjuvant combination chemotherapy regimens in treating patients who are receiving radiation therapy and fluorouracil either before or after surgery for stage II or stage III rectal cancer. Drugs used in chemotherapy, such as irinotecan, fluorouracil, leucovorin, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which adjuvant combination chemotherapy regimen is more effective in treating patients who are receiving radiation therapy and fluorouracil either before or after surgery for rectal cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
- To compare the overall survival of patients treated with irinotecan, 5-FU and leucovorin versus those treated with oxaliplatin, leucovorin and 5-FU versus those treated with leucovorin and 5-FU for patients with stage II and III rectal cancer.
SECONDARY OBJECTIVES:
-
To determine sphincter preservation, tolerance of treatment and patterns of failure.
-
To describe patterns of failures
OTHER PRE-SPECIFIED OBJECTIVES:
I.To prospectively assess rectal function using the Patient Bowel Function/Uniscale questionnaire and the FACT Diarrhea Subscale in patients treated with an adjuvant program of pelvic radiation therapy and chemotherapy.
- To correlate expression of key targets for 5-FU, leucovorin, oxaliplatin and irinotecan from tumor tissue biopsies with treatment efficacy III. To correlate tumor molecular prognostic markers with survival. IV. To determine physician preference in regard to the radiation-chemotherapy sequence in the Intergroup.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1), chemotherapy/radiotherapy sequence (preoperative vs postoperative), and risk group (high risk [T3, N+, M0 or T4, any N, M0] vs low risk [T1-2, N+, M0 or T3, N0, M0]). Patients are treated in 1 of 2 groups according to physician preference and then randomized to 1 of 3 treatment arms.
GROUP I (preoperative chemoradiotherapy and additional adjuvant chemotherapy): Preoperative chemoradiotherapy: Patients receive 1 of 3 treatment regimens, determined by the treating physician.
REGIMEN A (radiotherapy and fluorouracil): Patients undergo external beam radiotherapy once daily 5 days a week for 5 1/2 weeks (total of 28 fractions). Patients also receive concurrent fluorouracil intravenously (IV) continuously 7 days a week for 5 1/2 weeks.
REGIMEN B (radiotherapy, fluorouracil, and leucovorin calcium): Patients undergo external beam radiotherapy as in regimen A. Patients also receive concurrent fluorouracil IV and leucovorin calcium IV continuously for 4 days on weeks 1 and 5.
REGIMEN C (radiotherapy and capecitabine)*: Patients undergo external beam radiotherapy as in regimen A. Patients also receive concurrent oral capecitabine twice daily for 5 1/2 weeks.
NOTE: *Regimen C is allowed only for patients enrolled on protocol NSABP-R-04.
Surgery: Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection.
Additional adjuvant chemotherapy: Within 21-56 days after complete surgical resection, patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses.
ARM II: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses.
ARM III: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 8 weeks for 3 courses.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.
GROUP 2 (postoperative chemoradiotherapy and additional adjuvant chemotherapy): Within 21-56 days after complete surgical resection, patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive irinotecan, leucovorin calcium, and fluorouracil as in group 1, arm I for 4 courses.
ARM II: Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in group 1, arm II for 4 courses.
ARM III: Patients receive leucovorin calcium and fluorouracil as in group 1, arm III for 1 course.
Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemoradiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually for 5 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group I, Arm I Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Radiation: Radiotherapy
Undergo external beam radiation therapy
Other Names:
Drug: Fluorouracil
Given IV
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Irinotecan
Given IV
Other Names:
|
| Experimental: Group I, Arm II Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Radiation: Radiotherapy
Undergo external beam radiation therapy
Other Names:
Drug: Fluorouracil
Given IV
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Oxaliplatin
Given IV
Other Names:
|
| Experimental: Group I, Arm III Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 8 weeks for 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Radiation: Radiotherapy
Undergo external beam radiation therapy
Other Names:
Drug: Fluorouracil
Given IV
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
|
| Experimental: Group II, Arm I Patients receive irinotecan, leucovorin calcium, and fluorouracil as in group 1, arm I for 4 courses. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Radiation: Radiotherapy
Undergo external beam radiation therapy
Other Names:
Drug: Fluorouracil
Given IV
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Irinotecan
Given IV
Other Names:
|
| Experimental: Group II, Arm II Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in group 1, arm II for 4 courses. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Radiation: Radiotherapy
Undergo external beam radiation therapy
Other Names:
Drug: Fluorouracil
Given IV
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Oxaliplatin
Given IV
Other Names:
|
| Experimental: Group II, Arm III Patients receive leucovorin calcium and fluorouracil as in group 1, arm III for 1 course. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Radiation: Radiotherapy
Undergo external beam radiation therapy
Other Names:
Drug: Fluorouracil
Given IV
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 3-year Overall Survival Rate [assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years, estimated at 3 years]
Overall survival (OS) was defined as time from randomization to death from any cause. 3-year OS rate was estimated using Kaplan-Meier method.
Secondary Outcome Measures
- 3-year Disease Free Survival [assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years, estimated at 3 years]
Disease free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer and death from any cause, whichever occurred first. 3-year DFS rate was estimated using Kaplan-Meier method.
- Proportion of Sphincter Preservation [assessed at primary surgery time]
Proportion of sphincter preservation was defined as number of patients with sphincter preservation divided by total number of patients randomized to the arm
- Failure Pattern [assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years]
Type of failures (local/regional recurrence vs. distant recurrence vs. concurrent recurrence vs. second primary cancer vs. deaths) in the analysis population
Eligibility Criteria
Criteria
- Group I (Pre-operative) Registration
Inclusion Criteria:
-
Patients must have histologically proven adenocarcinoma of the rectum with no distant metastases. Clinical staging is required (T3N0M0, T4N0M0, TanyN1-3M0).
-
Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy.
-
The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 cm of anal verge by proctoscopic examination. In addition, patients who have had a portion of their tumors confirmed to be below the peritoneal reflection at the time of surgery are eligible regardless of the distance determined by endoscopy.
-
Transmural penetration of tumor through the muscularis propria must be demonstrated by CT scan, endo-rectal ultrasound or MRI.
-
Tumors must be defined prospectively by the surgeon as clinically resectable or not.
-
Clinically resectable tumors will be defined by the surgeon as not fixed and completely resectable with negative margins based on the routine examination of the non-anesthetized patient.
-
Before pre-op treatment, the surgeon should estimate and record the type of resection anticipated: APR, LAR or LAR/coloanal anastomosis.
-
The tumor may be clinically fixed or initially not completely resectable, clinical stage T4 N0-2 M0 based on the presence of at least one of the following criteria:
-
Clinically fixed tumors on rectal examination with tumor adherent to the pelvic sidewall or sacrum.
-
Hydronephrosis on CT scan or IVP or ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy, or invasion into prostate.
-
Vaginal or uterine involvement.
-
Patients must not have a previous or concurrent malignancy, with the exception of:
-
Nonmelanoma skin cancer or in situ cervical cancer.
-
Treated non-pelvic cancer from which the patient has been continuously disease-free for >5 years.
-
Patients must have ECOG performance status 0-1.
-
Patients must be > 18 years of age.
-
All females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy.
-
Sexually-active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
Exclusion Criteria:
-
Patients have received prior chemotherapy or pelvic irradiation therapy.
-
Female patients must not be pregnant or breast-feeding.
-
Patients have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy.
- Group II (Post-operative) Registration
Inclusion Criteria:
-
Patients must have had histologically proven adenocarcinoma of the rectum with no distant metastases. Pathologic staging is required (T3N0M0, T4N0M0, TanyN1-3M0).
-
Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy.
-
The distal border of the tumor must have been at or below the peritoneal reflection, defined as within 12 centimeters of anal verge by proctoscopic examination. In addition, patients who have had a portion of their tumors confirmed to be below the peritoneal reflection at the time of the surgery are eligible regardless of the distance determined by endoscopy.
-
Patients must not have received prior chemotherapy or pelvic irradiation therapy.
-
Patients must not have a previous or concurrent malignancy, with the exception of:
-
Non-melanoma skin cancer or in situ cervical cancer.
-
Treated non-pelvic cancer from which the patient has been continuously disease-free for >5 years.
-
Patients must have ECOG performance status 0-1.
-
Patients must be > 18 years of age.
-
All females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy.
-
Sexually active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception.
Exclusion Criteria:
-
Patients have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy.
-
Female patients are pregnant or breast-feeding.
- Randomization (Groups I and II)
Inclusion Criteria:
-
Patients must have a completely resected tumor and be within 21-56 days from the date of surgery.
-
Patients who received combination chemotherapy/XRT prior to randomization (Group I) must have had a minimum radiation dose of 50.4 Gy.
-
Patients must have ECOG performance status 0-1.
-
Patients must have adequate renal function (creatinine < 1.5 x ULN) obtained < 4 weeks prior to randomization.
-
Patients must have adequate hepatic function (bilirubin < 1.5 x ULN, SGOT (AST) < 3 x ULN) obtained < 4 weeks prior to randomization).
-
Patients must have absolute neutrophil count > 1500/mm3 and platelet count > 100,000/mm3 < 4 weeks prior to randomization.
Exclusion Criteria:
• Patients have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Eastern Cooperative Oncology Group | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Al Benson, Eastern Cooperative Oncology Group
Study Documents (Full-Text)
More Information
Publications
None provided.- NCI-2012-02959
- NCI-2012-02959
- E3201
- U10CA021115
Study Results
Participant Flow
| Recruitment Details | This study was activated on October 15, 2003. Accrual was suspended on November 26, 2004 and subsequently closed on October 25, 2005 with total accrual of 225 patients to step 1 and 179 patients to step 2. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group I, Arm S | Group II, Arm T | Group I, Arm I | Group I, Arm II | Group I, Arm III | Group II, Arm I | Group II, Arm II | Group II, Arm III |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Group I patients receive concurrent chemotherapy and radiation prior to surgery. | Patients who had surgery before registering to the study was in Group II. They were registered and randomized at the same time. | Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV Irinotecan: Given IV | Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV | Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 8 weeks for 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV | Patients receive irinotecan, leucovorin calcium, and fluorouracil as in group 1, arm I for 4 courses. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV Irinotecan: Given IV | Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in group 1, arm II for 4 courses. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV | Patients receive leucovorin calcium and fluorouracil as in group 1, arm III for 1 course. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV |
| Period Title: Step 1: Registration | ||||||||
| STARTED | 128 | 97 | 0 | 0 | 0 | 0 | 0 | 0 |
| Started Concurrent Chemo/Radiation | 125 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Reported AE Data | 123 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 88 | 96 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 40 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Step 1: Registration | ||||||||
| STARTED | 0 | 0 | 28 | 25 | 30 | 31 | 33 | 32 |
| Treated | 0 | 0 | 27 | 25 | 29 | 31 | 33 | 32 |
| Had Sphincter Preservation | 0 | 0 | 28 | 25 | 28 | 31 | 33 | 30 |
| Reported AE Data | 0 | 0 | 27 | 22 | 28 | 31 | 33 | 32 |
| COMPLETED | 0 | 0 | 18 | 13 | 21 | 25 | 29 | 24 |
| NOT COMPLETED | 0 | 0 | 10 | 12 | 9 | 6 | 4 | 8 |
Baseline Characteristics
| Arm/Group Title | Irinocetan (Arm I) | Oxaliplatin (Arm II) | Control (Arm III) | Total |
|---|---|---|---|---|
| Arm/Group Description | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received irinocetan plus 5-FU and leucovorin, | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received oxaliplatin plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group only received 5-FU and leucovorin. | Total of all reporting groups |
| Overall Participants | 59 | 58 | 62 | 179 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
58
|
56
|
58
|
57
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
19
32.2%
|
22
37.9%
|
19
30.6%
|
60
33.5%
|
| Male |
40
67.8%
|
36
62.1%
|
43
69.4%
|
119
66.5%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
2
3.2%
|
2
1.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
5.1%
|
1
1.7%
|
2
3.2%
|
6
3.4%
|
| White |
56
94.9%
|
57
98.3%
|
58
93.5%
|
171
95.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | 3-year Overall Survival Rate |
|---|---|
| Description | Overall survival (OS) was defined as time from randomization to death from any cause. 3-year OS rate was estimated using Kaplan-Meier method. |
| Time Frame | assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years, estimated at 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized patients |
| Arm/Group Title | Irinocetan (Arm I) | Oxaliplatin (Arm II) | Control (Arm III) |
|---|---|---|---|
| Arm/Group Description | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received irinocetan plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received oxaliplatin plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group only received 5-FU and leucovorin. |
| Measure Participants | 59 | 58 | 62 |
| Number (95% Confidence Interval) [proportion of patients] |
0.965
|
0.843
|
0.870
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Irinocetan (Arm I), Control (Arm III) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.35 |
| Comments | One-sided p value was reported | |
| Method | Log Rank | |
| Comments | stratified on ECOG performance status, clinical stage, timing of chemoradiotherapy, and regimen administration | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin (Arm II), Control (Arm III) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.69 |
| Comments | one-sided p value was reported | |
| Method | Log Rank | |
| Comments | stratified on ECOG performance status, clinical stage, timing of chemoradiaotherapy, regimen administration | |
| Title | 3-year Disease Free Survival |
|---|---|
| Description | Disease free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer and death from any cause, whichever occurred first. 3-year DFS rate was estimated using Kaplan-Meier method. |
| Time Frame | assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years, estimated at 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized patients |
| Arm/Group Title | Irinocetan (Arm I) | Oxaliplatin (Arm II) | Control (Arm III) |
|---|---|---|---|
| Arm/Group Description | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received irinocetan plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined.Patients in this group received oxaliplatin plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group only received 5-FU and leucovorin. |
| Measure Participants | 59 | 58 | 62 |
| Number (95% Confidence Interval) [proportion of patients] |
0.670
|
0.717
|
0.704
|
| Title | Proportion of Sphincter Preservation |
|---|---|
| Description | Proportion of sphincter preservation was defined as number of patients with sphincter preservation divided by total number of patients randomized to the arm |
| Time Frame | assessed at primary surgery time |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized patients |
| Arm/Group Title | Irinocetan (Arm I) | Oxaliplatin (Arm II) | Control (Arm III) |
|---|---|---|---|
| Arm/Group Description | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received irinocetan plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received oxaliplatin plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group only received 5-FU and leucovorin. |
| Measure Participants | 59 | 58 | 58 |
| Number (95% Confidence Interval) [proportion of patients] |
0.814
|
0.724
|
0.655
|
| Title | Failure Pattern |
|---|---|
| Description | Type of failures (local/regional recurrence vs. distant recurrence vs. concurrent recurrence vs. second primary cancer vs. deaths) in the analysis population |
| Time Frame | assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized patients |
| Arm/Group Title | Irinocetan (Arm I) | Oxaliplatin (Arm II) | Control (Arm III) |
|---|---|---|---|
| Arm/Group Description | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received irinocetan plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group received oxaliplatin plus 5-FU and leucovorin. | The study was not designed to look at the treatment regimen separately in the two groups. I in Group I and Group II are combined. Patients in this group only received 5-FU and leucovorin. |
| Measure Participants | 59 | 58 | 62 |
| Local/regional recurrence only |
3
5.1%
|
5
8.6%
|
5
8.1%
|
| Distant recurrence only |
15
25.4%
|
11
19%
|
10
16.1%
|
| Both local/regional and distant recurrence |
2
3.4%
|
4
6.9%
|
1
1.6%
|
| Any recurrence |
20
33.9%
|
20
34.5%
|
16
25.8%
|
| Second primary cancer |
3
5.1%
|
5
8.6%
|
2
3.2%
|
| Death |
19
32.2%
|
21
36.2%
|
21
33.9%
|
Adverse Events
| Time Frame | Assessed at the end of every cycle (1 cycle=2 weeks for Arm I and Arm II in both groups, 1 cycle=8 weeks for Arm III in both groups) while on treatment and for 30 days after the end of treatment, assessed up to 10 years | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Group 1 patients received concurrent chemotherapy and radiation in step 1, and then received the adjuvant therapy in step 2 after randomization. Adverse events were reported for step 1 (arm S) and step 2 (arms I,II,III) separately. Group 2 patients were registered and randomized at the same time, and adverse events for adjuvant therapy were reported at step 2 (arms I, II, III). | |||||||||||||
| Arm/Group Title | Arm S | Group I, Arm I | Group I, Arm II | Group I, Arm III | Group II, Arm I | Group II, Arm II | Group II, Arm III | |||||||
| Arm/Group Description | Preoperative chemo/radiation therapy received by Group I patients in step 1 | Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV Irinotecan: Given IV | Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV | Patients receive 1 of 3 preoperative chemo and radiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 8 weeks for 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV | Patients receive irinotecan, leucovorin calcium, and fluorouracil as in group 1, arm I for 4 courses. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV Irinotecan: Given IV | Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in group 1, arm II for 4 courses. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV | Patients receive leucovorin calcium and fluorouracil as in group 1, arm III for 1 course. Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemo and radiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III. Treatment continues in the absence of disease progression or unacceptable toxicity. Radiotherapy: Undergo external beam radiation therapy Fluorouracil: Given IV Leucovorin Calcium: Given IV | |||||||
All Cause Mortality |
||||||||||||||
| Arm S | Group I, Arm I | Group I, Arm II | Group I, Arm III | Group II, Arm I | Group II, Arm II | Group II, Arm III | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/123 (0.8%) | 8/27 (29.6%) | 12/22 (54.5%) | 11/28 (39.3%) | 11/31 (35.5%) | 9/33 (27.3%) | 10/32 (31.3%) | |||||||
Serious Adverse Events |
||||||||||||||
| Arm S | Group I, Arm I | Group I, Arm II | Group I, Arm III | Group II, Arm I | Group II, Arm II | Group II, Arm III | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 62/123 (50.4%) | 11/27 (40.7%) | 14/22 (63.6%) | 10/28 (35.7%) | 21/31 (67.7%) | 23/33 (69.7%) | 23/32 (71.9%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anemia | 2/123 (1.6%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 2/31 (6.5%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Hematologic-other | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Febrile neutropenia | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Cardiac disorders | ||||||||||||||
| Sinus tachycardia | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Cardiac-ischemia | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Colitis | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Diarrhea w/o prior colostomy | 32/123 (26%) | 3/27 (11.1%) | 2/22 (9.1%) | 6/28 (21.4%) | 12/31 (38.7%) | 10/33 (30.3%) | 16/32 (50%) | |||||||
| Enteritis | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Ileus | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 1/33 (3%) | 0/32 (0%) | |||||||
| Incontinence, anal | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Muco/stomatitis by exam, oral cavity | 5/123 (4.1%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Muco/stomatitis (symptom) oral cavity | 8/123 (6.5%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Muco/stomatitis (symptom) rectum | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Nausea | 4/123 (3.3%) | 3/27 (11.1%) | 0/22 (0%) | 2/28 (7.1%) | 2/31 (6.5%) | 1/33 (3%) | 3/32 (9.4%) | |||||||
| Obstruction, colon | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Obstruction, small bowel NOS | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Proctitis | 1/123 (0.8%) | 0/27 (0%) | 1/22 (4.5%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Vomiting | 3/123 (2.4%) | 1/27 (3.7%) | 1/22 (4.5%) | 1/28 (3.6%) | 3/31 (9.7%) | 0/33 (0%) | 3/32 (9.4%) | |||||||
| GI-other | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 1/33 (3%) | 1/32 (3.1%) | |||||||
| Abdomen, pain | 5/123 (4.1%) | 0/27 (0%) | 1/22 (4.5%) | 1/28 (3.6%) | 4/31 (12.9%) | 1/33 (3%) | 2/32 (6.3%) | |||||||
| Oral cavity, pain | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Rectum, pain | 6/123 (4.9%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| General disorders | ||||||||||||||
| Fatigue | 8/123 (6.5%) | 2/27 (7.4%) | 0/22 (0%) | 3/28 (10.7%) | 3/31 (9.7%) | 0/33 (0%) | 4/32 (12.5%) | |||||||
| Fever w/o neutropenia | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Pain NOS | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Pain-other | 2/123 (1.6%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Immune system disorders | ||||||||||||||
| Allergic reaction | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 2/33 (6.1%) | 0/32 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Infection w/ gr3-4 neut, abdomen NOS | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection w/ gr3-4 neut, pelvis NOS | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection w/ gr3-4 neut, urinary tract | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection Gr0-2 neut, abdomen | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection Gr0-2 neut, catheter | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Infection Gr0-2 neut, lung | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Infection Gr0-2 neut, penis | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection Gr0-2 neut, rectum | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection Gr0-2 neut, wound | 2/123 (1.6%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection w/ unk ANC rectum | 2/123 (1.6%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection Gr0-2 neut, blood | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Infection w/ unk ANC blood | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Radiation dermatitis | 3/123 (2.4%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Leak, incl. anastomotic, rectum | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Surgical hemorrhage | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Investigations | ||||||||||||||
| Leukocytes decreased | 2/123 (1.6%) | 4/27 (14.8%) | 4/22 (18.2%) | 2/28 (7.1%) | 3/31 (9.7%) | 5/33 (15.2%) | 3/32 (9.4%) | |||||||
| Lymphopenia | 8/123 (6.5%) | 0/27 (0%) | 4/22 (18.2%) | 1/28 (3.6%) | 2/31 (6.5%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Neutrophils decreased | 6/123 (4.9%) | 6/27 (22.2%) | 9/22 (40.9%) | 2/28 (7.1%) | 6/31 (19.4%) | 9/33 (27.3%) | 1/32 (3.1%) | |||||||
| Platelets decreased | 0/123 (0%) | 0/27 (0%) | 1/22 (4.5%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Weight loss | 0/123 (0%) | 2/27 (7.4%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| INR increased | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Alanine aminotransferase increased | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 1/33 (3%) | 0/32 (0%) | |||||||
| Blood bilirubin increased | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Creatinine increased | 1/123 (0.8%) | 1/27 (3.7%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Metabolic/Laboratory-other | 1/123 (0.8%) | 1/27 (3.7%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Anorexia | 6/123 (4.9%) | 1/27 (3.7%) | 0/22 (0%) | 3/28 (10.7%) | 2/31 (6.5%) | 1/33 (3%) | 4/32 (12.5%) | |||||||
| Dehydration | 6/123 (4.9%) | 1/27 (3.7%) | 0/22 (0%) | 4/28 (14.3%) | 2/31 (6.5%) | 1/33 (3%) | 2/32 (6.3%) | |||||||
| Acidosis | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Hyperglycemia | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Hyperkalemia | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 1/33 (3%) | 0/32 (0%) | |||||||
| Hypokalemia | 3/123 (2.4%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 2/33 (6.1%) | 2/32 (6.3%) | |||||||
| Hyponatremia | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Hyperuricemia | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Nonneuropathic generalized weakness | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Back, pain | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Extremity-limb, pain | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Neck, pain | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Ataxia | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Dizziness | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Neuropathy-motor | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Neuropathy-sensory | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 2/33 (6.1%) | 0/32 (0%) | |||||||
| Syncope | 0/123 (0%) | 1/27 (3.7%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Head/headache | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 1/33 (3%) | 1/32 (3.1%) | |||||||
| Neuropathic, pain | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Urethra, pain | 0/123 (0%) | 0/27 (0%) | 1/22 (4.5%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Incontinence urinary | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Renal failure | 0/123 (0%) | 1/27 (3.7%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Muco/stomatitis by exam, pharynx | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 1/33 (3%) | 0/32 (0%) | |||||||
| Muco/stomatitis (symptom) pharynx | 0/123 (0%) | 1/27 (3.7%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Throat/pharynx/larynx, pain | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| (ARDS) | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Cough | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Dyspnea | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||||||
| Hiccoughs | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Hypoxia | 0/123 (0%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Rash/desquamation | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Hand-foot reaction | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 2/31 (6.5%) | 1/33 (3%) | 2/32 (6.3%) | |||||||
| Vascular disorders | ||||||||||||||
| Hypotension | 1/123 (0.8%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Thrombosis/thrombus/embolism | 2/123 (1.6%) | 1/27 (3.7%) | 0/22 (0%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Arm S | Group I, Arm I | Group I, Arm II | Group I, Arm III | Group II, Arm I | Group II, Arm II | Group II, Arm III | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/123 (22%) | 7/27 (25.9%) | 3/22 (13.6%) | 3/28 (10.7%) | 6/31 (19.4%) | 6/33 (18.2%) | 12/32 (37.5%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anemia | 15/123 (12.2%) | 7/27 (25.9%) | 3/22 (13.6%) | 1/28 (3.6%) | 2/31 (6.5%) | 2/33 (6.1%) | 4/32 (12.5%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Diarrhea w/o prior colostomy | 10/123 (8.1%) | 4/27 (14.8%) | 1/22 (4.5%) | 1/28 (3.6%) | 3/31 (9.7%) | 3/33 (9.1%) | 5/32 (15.6%) | |||||||
| Muco/stomatitis by exam, oral cavity | 7/123 (5.7%) | 1/27 (3.7%) | 0/22 (0%) | 0/28 (0%) | 2/31 (6.5%) | 1/33 (3%) | 3/32 (9.4%) | |||||||
| Muco/stomatitis (symptom) oral cavity | 0/123 (0%) | 0/27 (0%) | 1/22 (4.5%) | 1/28 (3.6%) | 1/31 (3.2%) | 2/33 (6.1%) | 4/32 (12.5%) | |||||||
| Nausea | 10/123 (8.1%) | 4/27 (14.8%) | 3/22 (13.6%) | 1/28 (3.6%) | 1/31 (3.2%) | 3/33 (9.1%) | 6/32 (18.8%) | |||||||
| Vomiting | 0/123 (0%) | 2/27 (7.4%) | 0/22 (0%) | 1/28 (3.6%) | 2/31 (6.5%) | 2/33 (6.1%) | 1/32 (3.1%) | |||||||
| Abdomen, pain | 0/123 (0%) | 1/27 (3.7%) | 1/22 (4.5%) | 1/28 (3.6%) | 1/31 (3.2%) | 1/33 (3%) | 5/32 (15.6%) | |||||||
| General disorders | ||||||||||||||
| Fatigue | 13/123 (10.6%) | 3/27 (11.1%) | 3/22 (13.6%) | 1/28 (3.6%) | 3/31 (9.7%) | 4/33 (12.1%) | 8/32 (25%) | |||||||
| Investigations | ||||||||||||||
| Leukocytes decreased | 7/123 (5.7%) | 4/27 (14.8%) | 2/22 (9.1%) | 1/28 (3.6%) | 0/31 (0%) | 2/33 (6.1%) | 6/32 (18.8%) | |||||||
| Neutrophils decreased | 0/123 (0%) | 4/27 (14.8%) | 1/22 (4.5%) | 0/28 (0%) | 2/31 (6.5%) | 2/33 (6.1%) | 2/32 (6.3%) | |||||||
| Platelets decreased | 0/123 (0%) | 1/27 (3.7%) | 2/22 (9.1%) | 0/28 (0%) | 1/31 (3.2%) | 2/33 (6.1%) | 2/32 (6.3%) | |||||||
| Weight loss | 8/123 (6.5%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 0/32 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Anorexia | 0/123 (0%) | 1/27 (3.7%) | 2/22 (9.1%) | 1/28 (3.6%) | 0/31 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||||||
| Nervous system disorders | ||||||||||||||
| Neuropathy-sensory | 0/123 (0%) | 1/27 (3.7%) | 2/22 (9.1%) | 0/28 (0%) | 0/31 (0%) | 3/33 (9.1%) | 2/32 (6.3%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Rash/desquamation | 7/123 (5.7%) | 0/27 (0%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 1/33 (3%) | 2/32 (6.3%) | |||||||
| Hand-foot reaction | 0/123 (0%) | 2/27 (7.4%) | 0/22 (0%) | 0/28 (0%) | 0/31 (0%) | 0/33 (0%) | 2/32 (6.3%) | |||||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Statistician |
|---|---|
| Organization | ECOG-ACRIN statistical office |
| Phone | |
| eatrials@jimmy.harvard.edu |
- NCI-2012-02959
- NCI-2012-02959
- E3201
- U10CA021115