Epoetin Alfa or Darbepoetin Alfa in Treating Patients With Anemia Caused by Chemotherapy
Study Details
Study Description
Brief Summary
RATIONALE: Epoetin alfa and darbepoetin alfa may cause the body to make more red blood cells. They are used to treat anemia caused by chemotherapy in patients with cancer.
PURPOSE: This randomized clinical trial is studying four different schedules of epoetin alfa or darbepoetin alfa to compare how well they work in treating patients with anemia caused by chemotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
Primary
- Compare the relative efficacy of four different erythropoietic agent dosing schedules comprising epoetin alfa or darbepoetin alfa, in terms of the proportion of patients with chemotherapy-associated anemia who achieve a weekly and overall hematopoietic response.
Secondary
-
Compare the effect of these regimens on the mean hemoglobin increment measured weekly from baseline to 15 weeks in patients with a baseline hemoglobin of less than or equal to 10.5 g/dL.
-
Compare the time required to achieve hemoglobin levels within the goal range 11.0-12.0 g/dL in patients treated with these regimens.
-
Compare the effect of these regimens on the proportion of patients requiring red blood cell transfusions and on the number of transfusions required.
-
Compare the weekly change in hemoglobin in patients treated with these regimens.
-
Compare the need for dose reduction in patients treated with these regimens.
-
Compare the adverse event profiles of these regimens in these patients.
-
Compare quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, unblinded, pilot study. Patients are stratified according to severity of anemia (mild [hemoglobin ≥ 9.5 g/dL] vs severe [hemoglobin < 9.5 g/dL]), platinum-containing regimen (yes vs no), and tumor type (nonmyeloid hematologic malignancy vs solid tumor). Patients are randomized to 1 of 4 treatment arms.
-
Arm I: Patients receive epoetin alfa subcutaneously (SC) on day 1. Treatment repeats weekly for up to 15 courses in the absence of disease progression or unacceptable toxicity.
-
Arm II: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm I). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
-
Arm III: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm II). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
-
Arm IV: Patients receive darbepoetin alfa SC on day 1. Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
Hemoglobin levels are monitored throughout the study on a weekly basis and before each drug dose is administered. Drug dosing is adjusted (e.g., held, reduced, resumed at a lower dose) as needed to maintain hemoglobin values within the desired ranges.
Quality of life is assessed at baseline and at weeks 4, 7, 10, 13, and 16.
After completion of study treatment, patients are followed at 30 days.
PROJECTED ACCRUAL: A total of 320 patients will be accrued for this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Epoetin alfa - 40000 units 40,000 Units |
Drug: darbepoetin alfa
Drug: epoetin alfa
Procedure: fatigue assessment and management
Procedure: quality-of-life assessment
|
| Experimental: Epoetin alfa - 80000 units 80,000 Units |
Drug: darbepoetin alfa
Drug: epoetin alfa
Procedure: fatigue assessment and management
Procedure: quality-of-life assessment
|
| Experimental: Epoetin alfa - 120000 Units 120,000 Units |
Drug: darbepoetin alfa
Drug: epoetin alfa
Procedure: fatigue assessment and management
Procedure: quality-of-life assessment
|
| Experimental: Darbepoetin alfa*** 500 mcg |
Drug: darbepoetin alfa
Drug: epoetin alfa
Procedure: fatigue assessment and management
Procedure: quality-of-life assessment
|
Outcome Measures
Primary Outcome Measures
- The Percentage of Participants Who Exhibit a Hematopoietic Response [20 weeks]
A hematopoietic response was defined as Hb rise >2 g/dL from baseline or achieving Hb ≥ 11.5 g/dL, whichever occurs first, in the absence of RBC transfusions within 14 days of measurement) during the treatment period
Secondary Outcome Measures
- Weekly Change in Hemoglobin Levels [Baseline and Week 4, 7, 10, 13, 16]
To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa schedule
- Time Required to Achieve Hemoglobin Levels >= 11.5 g/dL [16 weeks]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule
- Mean Hemoglobin Change From Week 1 to Week 16 [Week 1 and Week 16]
To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa schedule. The positive numbers represent hemoglobin increases and negative numbers represent hemoglobin decreases.
- The Percentage of Participants Requiring Red Blood Cell (RBC) Transfusions [16 weeks]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule
- The Total RBC Transfusion Needed [16 weeks]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule
- The Percentage of Participants With Dose Omitted Due to Hematologic Reason [16 Weeks]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule
- The Percentage of Participants Reported Grade 3 or 4 Adverse Events [16 weeks]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Adverse events were measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
- Quality of Life as Measured by Functional Assessment of Cancer Therapy Scales for Anemia (FACT-AN) Over All Follow-up Evaluations [Weeks 4, 7, 10, 13 and 16]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. FACT-AN consist of Fatigue concerns subscale and non-fatigue concerns subscale. FACT Total Anemia score was calculated by adding the two subscales scores and transformed into 0-100 scale. FACT Total Anemia, Fatigue concerns scale and Non-Fatigue concerns scale are all ranges: 0 (Worst QOL) to 100 (Best QOL). Average scores across all time points for each subscale and total scale were calculated.
- Quality of Life as Measured by Linear Analogue Self Assessment Over All Follow-up Evaluation [Weeks 4, 7, 10, 13 and 16]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Linear Analogue Self Assessment (LASA) consists of 10 single-item numeric analogue scales on a scale of 0 to 10. Higher scores indicate better quality of life (QOL) on overall QOL, mental, physical, emotional spiritual QOL and Social activity; and constant pain, highest pain severity, level of fatigue and anxiety. Average scores across all time points for each item were calculated.
- Quality of Life as Measured by Brief Fatigue Inventory Overall All Follow-up Evaluations [Weeks 4, 7, 10, 13 and 16]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Brief Fatigue Inventory (BFI) consist of 3 single-item numeric analogue scales on a scale of 0 to 10; and an interference scale formed by 6 single-item numeric scales on a scale of 0 to 10. Higher scores indicate fatigue as bad as you can imagine for fatigue now, usual fatigue and worse fatigue; and completely interferes for BFI interference. Average scores across all time points for fatigue now, usual fatigue, worst fatigue and BFI interference subscale were calculated.
- Quality of Life as Measured by Symptom Distress Scale (SDS) Over All Follow-up Evaluations [Weeks 4, 7, 10, 13 and 16]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. SDS Scale range: 1 (No Symptom), 5 (Worst Symptom). Average scores across all time points for each item were calculated.
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Diagnosis of solid tumor or nonmyeloid hematologic malignancy (e.g., plasma cell dyscrasia or lymphoproliferative disorder)
-
No nonmelanomatous skin cancer
-
Hemoglobin ≤ 10.5 g/dL
-
Ferritin > 20 ng/mL (i.e., not obviously iron deficient)
-
Planning to receive ≥ 12 weeks of anticancer chemotherapy
-
Biological therapy (e.g., hypomethylating agents, monoclonal antibodies, or small molecule pathway inhibitors) with an individual or cumulative regimen incidence of grade 3 or 4 anemia > 10% is considered chemotherapy for purposes of this study
-
No known anemia secondary to any of the following:
-
Cyanocobalamin (vitamin B_12) or folic acid deficiency
-
Gastrointestinal bleeding within the past 2 weeks
-
Hemolysis
-
Myelodysplastic syndromes, myeloproliferative disorders, or acute myeloid leukemia
-
No primary hematologic disorder causing chronic moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major)
-
Carriers of these disease states allowed provided they are not anemic prior to cancer diagnosis
PATIENT CHARACTERISTICS:
-
ECOG performance status 0-2
-
Life expectancy ≥ 6 months
-
Not pregnant or nursing
-
No delivery of a baby of ≥ 18 weeks estimated gestational age within the past 3 months (90 days)
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
Weight > 40.0 kg and < 150.0 kg
-
No known hypersensitivity to epoetin alfa, darbepoetin alfa, mammalian-cell derived products, or human albumin
-
No uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 180 mm Hg and/or diastolic BP ≥ 100 mm Hg, despite medical therapy
-
No pulmonary emboli and/or deep vein thrombosis within the past 12 months
-
Patients actively receiving warfarin for a minimum of 4 weeks are exempted from this requirement
-
Prior superficial thrombophlebitis allowed
-
No cerebrovascular accident, ischemic stroke, acute coronary syndrome (e.g., unstable angina or Q-wave or non-Q wave myocardial infarction), or other arterial or venous thrombotic events within the past 6 months
-
No history of chronic hypercoagulable disorders (e.g., activated protein C resistance, anti-cardiolipin disorder, protein C deficiency, or protein S deficiency)
-
Patients receiving anticoagulation therapy (warfarin or acetylsalicyclic acid [aspirin] at a dose of ≥ 325 mg/day) for these conditions are eligible provided therapy is continued during the study period
-
History of previously treated seizures allowed provided the patient has been seizure-free for a minimum of 3 months
PRIOR CONCURRENT THERAPY:
-
See Disease Characteristics
-
More than 1 year since prior peripheral blood stem cell, bone marrow, or cord blood transplantation
-
More than 14 days since prior red blood cell transfusion
-
More than 14 days since prior major surgery, including, but not limited to, any of the following:
-
Amputation
-
Invasion of a body cavity or of the central nervous system using a scalpel, saw, or laser cutting tool
-
Resection of a body part (or parts), whether solid or liquid tissue or both, that includes ≥ 1% of a patient's preoperative weight
-
The following are not considered major surgery:
-
Diagnostic/therapeutic thoracentesis or paracentesis
-
Diagnostic skin biopsy
-
Digit or fingernail/thumbnail resection or laceration repair under local anesthesia
-
Diagnostic fat aspiration
-
Otic irrigation to remove cerumen impaction
-
Tympanocentesis
-
Uncomplicated dental extraction
-
Uncomplicated tonsillectomy
-
Laser corneal remodeling for refraction purposes
-
Cosmetic or therapeutic eyelid surgery
-
Bone marrow aspiration and biopsy
-
More than 10 weeks since prior darbepoetin alfa, epoetin alfa, or any investigational form of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis stimulating protein)
-
No planned stem cell transplantation within the next 4 months (18 weeks)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- Mayo Clinic
- National Cancer Institute (NCI)
Investigators
- Study Chair: Charles L. Loprinzi, M.D., Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000522677
- P30CA015083
- RC05CB
- 06-002991
- EPOANE3015
Study Results
Participant Flow
| Recruitment Details | Two hundred and thirty-nine (239) participants were enrolled at 10 Mayo Clinic Cancer Research Consortium (MCCRC) sites between February 2007 and December 2008. |
|---|---|
| Pre-assignment Detail | There were two canceled participants and 1 ineligible participants prior to study medication begins. These three participants were excluded from all analysis. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Period Title: Overall Study | ||||
| STARTED | 61 | 60 | 58 | 57 |
| COMPLETED | 39 | 33 | 40 | 40 |
| NOT COMPLETED | 22 | 27 | 18 | 17 |
Baseline Characteristics
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) | Total of all reporting groups |
| Overall Participants | 61 | 60 | 58 | 57 | 236 |
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
65.0
|
68.0
|
65.0
|
67.0
|
66.0
|
| Gender (Count of Participants) | |||||
| Female |
37
60.7%
|
24
40%
|
33
56.9%
|
42
73.7%
|
136
57.6%
|
| Male |
24
39.3%
|
36
60%
|
25
43.1%
|
15
26.3%
|
100
42.4%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
1
1.7%
|
0
0%
|
1
0.4%
|
| Asian |
0
0%
|
1
1.7%
|
1
1.7%
|
0
0%
|
2
0.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
4.9%
|
2
3.3%
|
4
6.9%
|
5
8.8%
|
14
5.9%
|
| White |
58
95.1%
|
57
95%
|
52
89.7%
|
52
91.2%
|
219
92.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
61
100%
|
60
100%
|
58
100%
|
57
100%
|
236
100%
|
| Anemia (participants) [Number] | |||||
| Mild: Hemoglobin of 9.5-11 |
45
73.8%
|
43
71.7%
|
43
74.1%
|
42
73.7%
|
173
73.3%
|
| Severe: Hemoglobin < 9.5 |
16
26.2%
|
17
28.3%
|
15
25.9%
|
15
26.3%
|
63
26.7%
|
| Platinum Containing Regimen (participants) [Number] | |||||
| Yes |
27
44.3%
|
27
45%
|
27
46.6%
|
25
43.9%
|
106
44.9%
|
| No |
34
55.7%
|
33
55%
|
31
53.4%
|
32
56.1%
|
130
55.1%
|
| Primary Tumor Type (participants) [Number] | |||||
| Hematologic |
5
8.2%
|
6
10%
|
5
8.6%
|
4
7%
|
20
8.5%
|
| Solid Tumor |
56
91.8%
|
54
90%
|
53
91.4%
|
53
93%
|
216
91.5%
|
| Height (cm) [Median (Full Range) ] | |||||
| Median (Full Range) [cm] |
167.6
|
168.0
|
165.2
|
166.5
|
167.0
|
| Baseline Hemoglobin (g/dL) [Median (Full Range) ] | |||||
| Median (Full Range) [g/dL] |
10.1
|
9.9
|
9.9
|
9.9
|
9.9
|
| Weight (kg) [Median (Full Range) ] | |||||
| Median (Full Range) [kg] |
69.1
|
72.6
|
70.6
|
71.0
|
71.3
|
Outcome Measures
| Title | The Percentage of Participants Who Exhibit a Hematopoietic Response |
|---|---|
| Description | A hematopoietic response was defined as Hb rise >2 g/dL from baseline or achieving Hb ≥ 11.5 g/dL, whichever occurs first, in the absence of RBC transfusions within 14 days of measurement) during the treatment period |
| Time Frame | 20 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Number [Percentage of participants] |
68.9
113%
|
61.7
102.8%
|
65.5
112.9%
|
66.7
117%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Epoetin Alfa - 40k Weekly, Epoetin Alfa - 80k Every 3 Weeks, Epoetin Alfa - 120k Every 3 Weeks, Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|
| Comments | With 80 patients per treatment arm, there will be> about 80% power to detect a difference through Fisher's exact test across two> treatment arms of 25% in the true percentage of patients that experience a> hematopoietic response as defined previously, if that percentage is at least 30% in> the superior group, again with a 1.7% type I error rate. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | If the hematopoietic response rate in the standard therapy group is far from 50% (<25% or >75%), the> above sample size will provide an 80% power to detect a difference as small as> 25%. | |
| Statistical Test of Hypothesis | p-Value | >0.41 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Weekly Change in Hemoglobin Levels |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa schedule |
| Time Frame | Baseline and Week 4, 7, 10, 13, 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol and had hemoglobin data at baseline, week 4, 7, 10, 13 or 16. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Week 4 Minus Baseline |
1.0
(1.26)
|
0.6
(1.02)
|
0.7
(1.21)
|
0.4
(1.21)
|
| Week 7 Minus Baseline |
1.7
(1.28)
|
1.0
(1.58)
|
1.1
(1.25)
|
1.5
(1.59)
|
| Week 10 Minus Baseline |
1.7
(1.39)
|
1.2
(1.42)
|
1.2
(1.37)
|
1.5
(1.44)
|
| Week 13 Minus Baseline |
2.1
(1.27)
|
1.2
(1.51)
|
1.3
(1.32)
|
1.6
(1.65)
|
| Week 16 Minus Baseline |
1.7
(1.67)
|
1.2
(1.64)
|
1.6
(1.44)
|
1.9
(1.41)
|
| Title | Time Required to Achieve Hemoglobin Levels >= 11.5 g/dL |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol and had hemoglobin levels data. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Median (95% Confidence Interval) [days] |
32
|
50
|
49
|
49
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Epoetin Alfa - 40k Weekly, Epoetin Alfa - 80k Every 3 Weeks, Epoetin Alfa - 120k Every 3 Weeks, Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 80 patients per arm will provide> 80% power to detect differences between average hemoglobin levels in the> reference arm and another treatment of 50% of the standard deviation. Note that> typically one would expect the estimates for the standard deviation at a single time> point to differ from the standard deviation for the difference from baseline. | |
| Statistical Test of Hypothesis | p-Value | >0.13 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Mean Hemoglobin Change From Week 1 to Week 16 |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa schedule. The positive numbers represent hemoglobin increases and negative numbers represent hemoglobin decreases. |
| Time Frame | Week 1 and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol and had hemoglobin data. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Mean (Standard Deviation) [g/dL] |
11.0
(1.03)
|
10.3
(1.04)
|
10.6
(0.8)
|
10.7
(0.96)
|
| Title | The Percentage of Participants Requiring Red Blood Cell (RBC) Transfusions |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol and had RBC transfusions data. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Number [percentage of participants] |
27.9
45.7%
|
33.3
55.5%
|
22.4
38.6%
|
29.8
52.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Epoetin Alfa - 40k Weekly, Epoetin Alfa - 80k Every 3 Weeks, Epoetin Alfa - 120k Every 3 Weeks, Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|
| Comments | With 80 patients per treatment arm, there will be> about 80% power to detect a difference through Fisher's exact test across two> treatment arms of 25% in the true percentage of patients that experience a> hematopoietic response as defined previously, if that percentage is at least 30% in> the superior group, again with a 1.7% type I error rate. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | If the hematopoietic response rate in the standard therapy group is far from 50% (<25% or >75%), the> above sample size will provide an 80% power to detect a difference as small as> 25%. | |
| Statistical Test of Hypothesis | p-Value | >0.49 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | The Total RBC Transfusion Needed |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol and had RBC transfusions data. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Mean (Standard Deviation) [g/dL] |
1.1
(2.33)
|
1.2
(2.67)
|
0.6
(1.20)
|
1.1
(2.31)
|
| Title | The Percentage of Participants With Dose Omitted Due to Hematologic Reason |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule |
| Time Frame | 16 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Number [percentage of Participants] |
63.9
104.8%
|
30
50%
|
34.5
59.5%
|
45.6
80%
|
| Title | The Percentage of Participants Reported Grade 3 or 4 Adverse Events |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Adverse events were measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol and reported at least one value after baseline. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 60 | 60 | 58 | 55 |
| Number [percentage of participants] |
22
36.1%
|
22
36.7%
|
17
29.3%
|
13
22.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Epoetin Alfa - 40k Weekly, Epoetin Alfa - 80k Every 3 Weeks, Epoetin Alfa - 120k Every 3 Weeks, Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|
| Comments | With 80 patients per treatment arm, there will be about 80% power to detect a difference through Fisher's exact test across two treatment arms of 25% in the true percentage of patients that experience a hematopoietic response as defined previously, if that percentage is at least 30% in the superior group, again with a 1.7% type I error rate. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | If the hematopoietic response rate in the standard therapy group is far from 50% (<25% or >75%), the above sample size will provide an 80% power to detect a difference as small as 25%. | |
| Statistical Test of Hypothesis | p-Value | >0.56 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Quality of Life as Measured by Functional Assessment of Cancer Therapy Scales for Anemia (FACT-AN) Over All Follow-up Evaluations |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. FACT-AN consist of Fatigue concerns subscale and non-fatigue concerns subscale. FACT Total Anemia score was calculated by adding the two subscales scores and transformed into 0-100 scale. FACT Total Anemia, Fatigue concerns scale and Non-Fatigue concerns scale are all ranges: 0 (Worst QOL) to 100 (Best QOL). Average scores across all time points for each subscale and total scale were calculated. |
| Time Frame | Weeks 4, 7, 10, 13 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol with QOL data. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| FACT Fatigue Concerns |
48.6
(17.13)
|
52.0
(20.75)
|
52.6
(23.12)
|
49.8
(19.66)
|
| FACT Nonfatigue Concerns |
60.6
(13.08)
|
62.2
(16.64)
|
61.3
(16.27)
|
59.4
(13.39)
|
| FACT Total Anemia |
52.8
(14.58)
|
55.6
(18.08)
|
55.6
(19.85)
|
53.1
(16.24)
|
| Title | Quality of Life as Measured by Linear Analogue Self Assessment Over All Follow-up Evaluation |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Linear Analogue Self Assessment (LASA) consists of 10 single-item numeric analogue scales on a scale of 0 to 10. Higher scores indicate better quality of life (QOL) on overall QOL, mental, physical, emotional spiritual QOL and Social activity; and constant pain, highest pain severity, level of fatigue and anxiety. Average scores across all time points for each item were calculated. |
| Time Frame | Weeks 4, 7, 10, 13 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol with QOL data. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Overall QOL |
6.4
(1.59)
|
6.5
(2.00)
|
6.6
(2.17)
|
6.1
(1.61)
|
| Mental QOL |
6.9
(1.80)
|
7.0
(1.97)
|
7.2
(1.91)
|
6.5
(1.39)
|
| Physical QOL |
5.7
(1.54)
|
5.8
(2.11)
|
5.9
(2.22)
|
5.8
(1.65)
|
| Emotional QOL |
6.5
(1.68)
|
6.8
(1.99)
|
6.7
(2.03)
|
6.3
(1.80)
|
| Social Activity Level |
5.5
(2.08)
|
5.5
(2.12)
|
5.4
(2.34)
|
5.1
(2.01)
|
| Spiritual QOL |
7.4
(1.54)
|
7.4
(1.81)
|
7.3
(2.07)
|
6.8
(1.99)
|
| Pain Frequency |
4.5
(2.46)
|
4.3
(2.96)
|
3.9
(3.02)
|
4.2
(2.42)
|
| Pain Severity |
4.1
(2.16)
|
3.8
(2.72)
|
3.7
(2.88)
|
4.0
(2.24)
|
| Fatigue |
5.6
(1.59)
|
5.5
(2.02)
|
5.6
(2.14)
|
5.4
(1.60)
|
| Anxiety |
4.1
(1.81)
|
3.9
(2.20)
|
4.6
(2.36)
|
4.2
(1.67)
|
| Title | Quality of Life as Measured by Brief Fatigue Inventory Overall All Follow-up Evaluations |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Brief Fatigue Inventory (BFI) consist of 3 single-item numeric analogue scales on a scale of 0 to 10; and an interference scale formed by 6 single-item numeric scales on a scale of 0 to 10. Higher scores indicate fatigue as bad as you can imagine for fatigue now, usual fatigue and worse fatigue; and completely interferes for BFI interference. Average scores across all time points for fatigue now, usual fatigue, worst fatigue and BFI interference subscale were calculated. |
| Time Frame | Weeks 4, 7, 10, 13 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol with QOL data. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Fatigue Now |
4.8
(2.25)
|
4.6
(2.44)
|
4.6
(2.53)
|
4.7
(2.25)
|
| Usual Fatigue |
4.7
(2.12)
|
4.7
(2.40)
|
4.7
(2.53)
|
4.7
(2.24)
|
| Worst Fatigue |
5.5
(2.17)
|
5.6
(2.54)
|
5.4
(2.60)
|
5.3
(2.43)
|
| BFI Interference |
4.3
(1.95)
|
4.1
(2.42)
|
4.3
(2.60)
|
4.4
(2.17)
|
| Title | Quality of Life as Measured by Symptom Distress Scale (SDS) Over All Follow-up Evaluations |
|---|---|
| Description | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. SDS Scale range: 1 (No Symptom), 5 (Worst Symptom). Average scores across all time points for each item were calculated. |
| Time Frame | Weeks 4, 7, 10, 13 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were evaluable per protocol with QOL data. |
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks |
|---|---|---|---|---|
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) |
| Measure Participants | 61 | 60 | 58 | 57 |
| Nausea Frequency |
1.6
(0.64)
|
1.5
(0.67)
|
1.6
(0.56)
|
1.6
(0.73)
|
| Nausea Severity |
1.5
(0.59)
|
1.4
(0.62)
|
1.4
(0.61)
|
1.6
(0.73)
|
| Appetite |
2.3
(0.96)
|
2.3
(0.94)
|
2.2
(0.98)
|
2.4
(0.91)
|
| Insomnia |
2.4
(0.99)
|
2.0
(0.88)
|
2.3
(0.89)
|
2.4
(0.91)
|
| Pain Frequency |
2.7
(1.12)
|
2.5
(1.15)
|
2.4
(1.22)
|
2.7
(1.16)
|
| Pain Severity |
2.2
(0.97)
|
2.0
(1.02)
|
2.0
(1.05)
|
2.1
(0.88)
|
| Fatigue |
3.1
(0.82)
|
3.0
(0.94)
|
2.8
(0.97)
|
2.9
(0.91)
|
| Bowel |
2.2
(1.00)
|
2.4
(1.20)
|
2.3
(1.05)
|
2.3
(0.95)
|
| Concentration |
2.2
(0.99)
|
2.0
(1.00)
|
1.9
(0.89)
|
2.2
(0.96)
|
| Appearance |
2.1
(0.89)
|
2.2
(1.05)
|
2.0
(1.09)
|
2.2
(0.97)
|
| Breathing |
1.5
(0.54)
|
1.6
(0.64)
|
1.6
(0.82)
|
1.7
(1.01)
|
| Outlook |
2.2
(0.98)
|
2.1
(0.99)
|
2.1
(0.91)
|
2.4
(1.02)
|
| Cough |
1.8
(0.77)
|
1.7
(0.66)
|
1.8
(0.69)
|
2.0
(0.84)
|
| Depression |
1.8
(0.64)
|
1.7
(0.79)
|
1.8
(0.65)
|
2.0
(0.90)
|
Adverse Events
| Time Frame | 16 Weeks | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All evaluable patients per protocol that reported at least one value after baseline. | |||||||
| Arm/Group Title | Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks | ||||
| Arm/Group Description | Patients receive Epoetin alfa 40,000 units subcutaneously every week for 15 weeks (15 doses) | Patients receive Epoetin alfa 80,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Epoetin alfa 120,000 units subcutaneously every 3 weeks for 15 weeks (5 doses) | Patients receive Darbepoetin alfa 500 micrograms (mcg) subcutaneously every 3 weeks for 15 weeks (5 doses) | ||||
All Cause Mortality |
||||||||
| Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/60 (6.7%) | 7/60 (11.7%) | 4/58 (6.9%) | 2/56 (3.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Diarrhea | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Rectal stenosis | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| General disorders | ||||||||
| Disease progression | 2/60 (3.3%) | 2 | 2/60 (3.3%) | 2 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Sudden death | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Infections and infestations | ||||||||
| Pneumonia | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Investigations | ||||||||
| Neutrophil count decreased | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 1/60 (1.7%) | 1 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Dehydration | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Hyponatremia | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscle weakness | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Renal and urinary disorders | ||||||||
| Hemorrhage urinary tract | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnea | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Hypoxia | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Vascular disorders | ||||||||
| Hypertension | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Thrombosis | 1/60 (1.7%) | 1 | 1/60 (1.7%) | 1 | 2/58 (3.4%) | 2 | 1/56 (1.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| Epoetin Alfa - 40k Weekly | Epoetin Alfa - 80k Every 3 Weeks | Epoetin Alfa - 120k Every 3 Weeks | Darbepoetin Alfa - 500 mcg Every 3 Weeks | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/60 (35%) | 16/60 (26.7%) | 16/58 (27.6%) | 7/56 (12.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Hemoglobin decreased | 0/60 (0%) | 0 | 5/60 (8.3%) | 6 | 3/58 (5.2%) | 3 | 2/56 (3.6%) | 3 |
| Cardiac disorders | ||||||||
| Atrial flutter | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Atrial tachycardia | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Left ventricular failure | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Myocardial ischemia | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Eye disorders | ||||||||
| Extraocular muscle paresis | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 1/60 (1.7%) | 1 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Colonic hemorrhage | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Constipation | 2/60 (3.3%) | 2 | 1/60 (1.7%) | 1 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Diarrhea | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 2/58 (3.4%) | 3 | 0/56 (0%) | 0 |
| Dysphagia | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Flatulence | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Mucositis oral | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Nausea | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 2/58 (3.4%) | 2 | 0/56 (0%) | 0 |
| Rectal hemorrhage | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Toothache | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Vomiting | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| General disorders | ||||||||
| Chest pain | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Disease progression | 1/60 (1.7%) | 1 | 1/60 (1.7%) | 1 | 3/58 (5.2%) | 3 | 1/56 (1.8%) | 1 |
| Fatigue | 3/60 (5%) | 3 | 4/60 (6.7%) | 12 | 4/58 (6.9%) | 6 | 1/56 (1.8%) | 1 |
| Pain | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Infections and infestations | ||||||||
| Bladder infection | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Colitis, infectious (e.g., Clostridium difficile) | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Infectious meningitis | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Pneumonia | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Sepsis | 2/60 (3.3%) | 3 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Sinusitis | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Tooth infection | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Wound infection | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Investigations | ||||||||
| Activated partial thromboplastin time prolonged | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| CD4 lymphocytes decreased | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| INR increased | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 5 | 0/56 (0%) | 0 |
| Leukocyte count decreased | 0/60 (0%) | 0 | 2/60 (3.3%) | 3 | 1/58 (1.7%) | 1 | 1/56 (1.8%) | 1 |
| Lymphocyte count decreased | 0/60 (0%) | 0 | 2/60 (3.3%) | 5 | 2/58 (3.4%) | 4 | 0/56 (0%) | 0 |
| Neutrophil count decreased | 0/60 (0%) | 0 | 3/60 (5%) | 4 | 1/58 (1.7%) | 1 | 2/56 (3.6%) | 2 |
| Platelet count decreased | 0/60 (0%) | 0 | 4/60 (6.7%) | 5 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Weight loss | 0/60 (0%) | 0 | 1/60 (1.7%) | 2 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Acidosis | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Anorexia | 1/60 (1.7%) | 1 | 2/60 (3.3%) | 3 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Dehydration | 0/60 (0%) | 0 | 2/60 (3.3%) | 2 | 1/58 (1.7%) | 1 | 2/56 (3.6%) | 2 |
| Hypoalbuminemia | 0/60 (0%) | 0 | 1/60 (1.7%) | 2 | 0/58 (0%) | 0 | 2/56 (3.6%) | 2 |
| Hypocalcemia | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Hypokalemia | 0/60 (0%) | 0 | 1/60 (1.7%) | 2 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Hyponatremia | 1/60 (1.7%) | 1 | 1/60 (1.7%) | 2 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 2/58 (3.4%) | 2 | 0/56 (0%) | 0 |
| Muscle weakness | 0/60 (0%) | 0 | 2/60 (3.3%) | 2 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Muscle weakness lower limb | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Headache | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Mini mental status examination abnormal | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Peripheral motor neuropathy | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Peripheral sensory neuropathy | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Syncope | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Confusion | 0/60 (0%) | 0 | 0/60 (0%) | 0 | 2/58 (3.4%) | 2 | 0/56 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Renal failure | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 1/56 (1.8%) | 1 |
| Renal pelvis fistula | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnea | 0/60 (0%) | 0 | 3/60 (5%) | 4 | 1/58 (1.7%) | 1 | 2/56 (3.6%) | 2 |
| Hemorrhage nasal | 0/60 (0%) | 0 | 2/60 (3.3%) | 2 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Pneumonitis | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/56 (0%) | 0 |
| Respiratory disorder | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Hand-and-foot syndrome | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Skin disorder | 0/60 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Vascular disorders | ||||||||
| Hypertension | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 1/56 (1.8%) | 1 |
| Peripheral ischemia | 1/60 (1.7%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/56 (0%) | 0 |
| Thrombosis | 5/60 (8.3%) | 5 | 0/60 (0%) | 0 | 2/58 (3.4%) | 2 | 0/56 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Charles L. Loprinzi, M.D. |
|---|---|
| Organization | Mayo Clinic |
| Phone | 507-266-6247 |
| loprinzi.charles@mayo.edu |
- CDR0000522677
- P30CA015083
- RC05CB
- 06-002991
- EPOANE3015