Stereotactic Body Radiation Therapy in Treating Patients With Inoperable Stage I or Stage II Non-Small Cell Lung Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00087438
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 59
• Locations: 2
• Arm: 1
• Duration (Months): 151
• Patients Per Site: 29.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Stereotactic body radiation therapy may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue.

PURPOSE: This phase II trial is studying how well stereotactic body radiation therapy works in treating patients with inoperable stage I or stage II non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Radiation: stereotactic body radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine whether treatment with stereotactic body radiotherapy results in acceptable local control (i.e., ≥ 80%) in patients with medically inoperable stage I or II non-small cell lung cancer.

Secondary

• Determine treatment-related toxicity in patients treated with this therapy.

• Determine disease-free survival, overall survival, and patterns of failure in patients treated with this therapy.

OUTLINE: This is a multicenter study.

Patients receive 3 fractions of stereotactic body radiotherapy over 8-14 days in the absence of disease progression or unacceptable toxicity.

Patients are followed up at 6 and 12 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 26 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients With Medically Inoperable Stage I/II Non-Small Cell Lung Cancer
• Study Start Date: May 1, 2004
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stereotactic body radiation therapy (SBRT) 20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy	Radiation: stereotactic body radiation therapy

Outcome Measures

Primary Outcome Measures

1. Local Control at 2 Years [From the start of treatment to 2 years]

   Local control is defined as absence of local failure, which is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Local control time is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local failure (censored). Rates are estimated using the Kaplan-Meier method.

Secondary Outcome Measures

1. Proportion of Subjects With Specified Adverse Events [From randomization to last follow-up. Analysis occurred after all patients had been on study for at least 2 years. Maximum follow-up at time of analysis was 4.2 years.]

   Specified adverse events are defined as any treatment-related adverse events that are grade 4, grade 5, or any of the following treatment-related grade 3 adverse events: Gastrointestinal: dysphagia, esophagitis, esophageal stricture, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, cardiomyopathy, ventricular dysfunction; Neurologic: myelitis, neuropathy (cranial and motor) Hemorrhage: pulmonary or upper respiratory Pulmonary: decline in pulmonary function as measured by pulmonary function tests, pneumonitis, pulmonary fibrosis, hypoxemia, pleural effusion. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

2. Rate of Local Recurrence at 2 Years [From the start of treatment to 2 years]

   Local failure is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Time to local recurrence is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local recurrence (censored).

3. Rate of Regional Recurrence at 2 Years [From the start of treatment to 2 years]

   Regional recurrence is defined as hilar, mediastinal, and supraclavicular nodal failure.Time to regional recurrence is defined as time from start of treatment to the date of first regional recurrence, last known follow-up (censored), or death without regional recurrence (competing risk). Rates are estimated using the cumulative incidence method.

4. Rate of Disseminated Recurrence at 2 Years [From the start of treatment to 2 years]

   Disseminated recurrence is defined as uninvolved lobe failures and failures beyond the lungs and regional lymph nodes. Time to disseminated recurrence is defined as time from start of treatment to the the date of disseminated recurrence, last known follow-up (censored), or death without disseminated recurrence (competing risk). Rates are estimated using the cumulative incidence method.

5. Rate of Disease-free Survival at 2 Years [From the start of treatment to 2 years]

   Disease is defined as local or regional progression or development of distant metastases. Disease-free survival time is defined as time from start of treatment to the date of disease, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.

6. Rate of Overall Survival at 2 Years [From the start of treatment to 2 years]

   Overall survival time is defined as time from start of treatment to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

• The following primary cancer subtypes are eligible:

• Squamous cell carcinoma

• Adenocarcinoma

• Large cell carcinoma

• Bronchoalveolar cell carcinoma

• Non-small cell carcinoma not otherwise specified

• Stage I or II disease based on 1 of the following tumor node metastasis (TNM) stage criteria:

• T1, N0, M0

• T2 (≤ 5 cm), N0, M0

• T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only)

• No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree* NOTE: *Defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, and right and left lower lobe bronchi)

• No primary T3 tumors involving the central chest (≤ 2 cm toward carina invasion) or structures of the mediastinum

• Any hilar or mediastinal lymph nodes > 1 cm on CT scan OR demonstrating suspicious uptake on positron-emission tomography scan must be biopsied and confirmed negative for NSCLC

• The primary tumor must be deemed technically resectable with a reasonable possibility of obtaining a gross total resection with negative margins (defined as a potentially curative resection (PCR))

• Deemed medically inoperable based on pulmonary function for surgical resection of NSCLC secondary to an underlying physiological problem, including any of the following medical conditions*:

• Baseline forced expiratory volume (FEV)_1< 40% of predicted

• Postoperative predicted FEV_1 < 30% of predicted

• Severely reduced diffusion capacity

• Baseline hypoxemia and/or hypercapnia

• Exercise oxygen consumption < 50% of predicted

• Severe pulmonary hypertension

• Diabetes mellitus with severe end organ damage

• Severe cerebral, cardiac, or peripheral vascular disease

• Severe chronic heart disease NOTE: *Patients who refuse a PCR due to preference, ideology, emotional or psychological issues, mental illness, or inability to give informed consent are not eligible

• No evidence of regional or distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• See Disease Characteristics

• No active pericardial infection

Pulmonary

• See Disease Characteristics

• No active pulmonary infection

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No active systemic infection

• No other concurrent illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent biologic therapy

• No concurrent vaccine therapy

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior lung or mediastinal radiotherapy

• No concurrent standard fractionated radiotherapy

• No concurrent intensity modulated radiotherapy

• No concurrent cobalt-60 or charged particle beams (including electrons, protons, or heavier ions)

Surgery

• See Disease Characteristics

• No concurrent surgery

Other

• No other concurrent antineoplastic therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
2	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Robert D. Timmerman, MD, Simmons Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Hurkmans CW, Cuijpers JP, Lagerwaard FJ, Widder J, van der Heide UA, Schuring D, Senan S. Dosimetric evaluation of heterogeneity corrections for RTOG 0236: stereotactic body radiotherapy of inoperable Stage I-II non-small-cell lung cancer. In reply to Dr. Xiao et al. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):318; author reply 318. doi: 10.1016/j.ijrobp.2009.05.050.
• Timmerman R, Galvin J, Michalski J, Straube W, Ibbott G, Martin E, Abdulrahman R, Swann S, Fowler J, Choy H. Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer. Acta Oncol. 2006;45(7):779-86. Review.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00087438
• Other Study ID Numbers: RTOG-0236; CDR0000371578
• First Posted: Jul 12, 2004
• Last Update Posted: Jan 16, 2019
• Last Verified: Dec 1, 2018

• Keywords provided by Radiation Therapy Oncology Group: stage I non-small cell lung cancer; stage II non-small cell lung cancer; squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

Participant Flow

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy stereotactic body radiation therapy
Period Title: Overall Study
STARTED	59
COMPLETED	55
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy stereotactic body radiation therapy
Overall Participants	55
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	72
Sex: Female, Male (Count of Participants)
Female	34 61.8%
Male	21 38.2%

Outcome Measures

1. Primary Outcome

Title	Local Control at 2 Years
Description	Local control is defined as absence of local failure, which is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Local control time is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local failure (censored). Rates are estimated using the Kaplan-Meier method.
Time Frame	From the start of treatment to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients who started protocol treatment.

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy stereotactic body radiation therapy
Measure Participants	55
Number (95% Confidence Interval) [percentage of subjects]	97.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stereotactic Body Radiation Therapy (SBRT)
	Comments	Null hypothesis = 60% two-year local control (0.02128/mo. hazard rate); alternative = 80% (0.0093/mo.) assuming at least approximately exponential distribution of time to local progression. Using the asymptotic properties of the ratio of the logarithms of hazard rates, less than 18 cases of local progression were required for a Type I error rate of 0.05 with 80% power to detect a difference in local control rates at least this large. Hazard rate estimated using life table two-year estimates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	Test statistic = [ln(estimated hazard rate) - ln(hypothesized hazard rates)] / [1/square root (number of patients with local progression by two years]. Reject null hypothesis at an alpha level of 0.05 if test statistics is less than -1.645.
	Method	z-test, one-sided
	Comments

2. Secondary Outcome

Title	Proportion of Subjects With Specified Adverse Events
Description	Specified adverse events are defined as any treatment-related adverse events that are grade 4, grade 5, or any of the following treatment-related grade 3 adverse events: Gastrointestinal: dysphagia, esophagitis, esophageal stricture, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, cardiomyopathy, ventricular dysfunction; Neurologic: myelitis, neuropathy (cranial and motor) Hemorrhage: pulmonary or upper respiratory Pulmonary: decline in pulmonary function as measured by pulmonary function tests, pneumonitis, pulmonary fibrosis, hypoxemia, pleural effusion. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Time Frame	From randomization to last follow-up. Analysis occurred after all patients had been on study for at least 2 years. Maximum follow-up at time of analysis was 4.2 years.

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy stereotactic body radiation therapy
Measure Participants	55
Count of Participants [Participants]	9 16.4%

3. Secondary Outcome

Title	Rate of Local Recurrence at 2 Years
Description	Local failure is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Time to local recurrence is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local recurrence (censored).
Time Frame	From the start of treatment to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	2.4 4.4%

4. Secondary Outcome

Title	Rate of Regional Recurrence at 2 Years
Description	Regional recurrence is defined as hilar, mediastinal, and supraclavicular nodal failure.Time to regional recurrence is defined as time from start of treatment to the date of first regional recurrence, last known follow-up (censored), or death without regional recurrence (competing risk). Rates are estimated using the cumulative incidence method.
Time Frame	From the start of treatment to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	0 0%

5. Secondary Outcome

Title	Rate of Disseminated Recurrence at 2 Years
Description	Disseminated recurrence is defined as uninvolved lobe failures and failures beyond the lungs and regional lymph nodes. Time to disseminated recurrence is defined as time from start of treatment to the the date of disseminated recurrence, last known follow-up (censored), or death without disseminated recurrence (competing risk). Rates are estimated using the cumulative incidence method.
Time Frame	From the start of treatment to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	11.1 20.2%

6. Secondary Outcome

Title	Rate of Disease-free Survival at 2 Years
Description	Disease is defined as local or regional progression or development of distant metastases. Disease-free survival time is defined as time from start of treatment to the date of disease, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.
Time Frame	From the start of treatment to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	67.3 122.4%

7. Secondary Outcome

Title	Rate of Overall Survival at 2 Years
Description	Overall survival time is defined as time from start of treatment to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Time Frame	From the start of treatment to 2 years

Outcome Measure Data

Analysis Population Description

Eligible patients

Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	72.7 132.2%

Adverse Events

Adverse Event Reporting Description	Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Arm/Group Title	Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy stereotactic body radiation therapy
All Cause Mortality
	Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	11/55 (20%)
Blood and lymphatic system disorders
Lymphatics - Other	1/55 (1.8%)
Cardiac disorders
Cardiac general - Other	1/55 (1.8%)
Gastrointestinal disorders
Constipation	1/55 (1.8%)
Dysphagia	1/55 (1.8%)
General disorders
Chest pain	1/55 (1.8%)
Fatigue	8/55 (14.5%)
Investigations
Forced expiratory volume	1/55 (1.8%)
Metabolic/laboratory - Other	1/55 (1.8%)
Weight decreased	1/55 (1.8%)
Metabolism and nutrition disorders
Anorexia	2/55 (3.6%)
Hyperglycemia NOS	1/55 (1.8%)
Psychiatric disorders
Insomnia	1/55 (1.8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/55 (5.5%)
Dyspnea	7/55 (12.7%)
Pneumonitis NOS	1/55 (1.8%)
Pulmonary hypertension NOS	1/55 (1.8%)
Pulmonary/upper respiratory - Other	1/55 (1.8%)
Other (Not Including Serious) Adverse Events
	Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	49/55 (89.1%)
Blood and lymphatic system disorders
Blood/bone marrow - Other	6/55 (10.9%)
Hemoglobin	13/55 (23.6%)
Cardiac disorders
Atrial fibrillation	3/55 (5.5%)
Gastrointestinal disorders
Abdominal pain NOS	4/55 (7.3%)
Diarrhea NOS	3/55 (5.5%)
Nausea	8/55 (14.5%)
Vomiting NOS	5/55 (9.1%)
General disorders
Chest pain	8/55 (14.5%)
Edema: limb	4/55 (7.3%)
Fatigue	21/55 (38.2%)
Pain - Other	3/55 (5.5%)
Pyrexia	3/55 (5.5%)
Rigors	3/55 (5.5%)
Infections and infestations
Infection with Grade 3 or 4 neutrop	3/55 (5.5%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	6/55 (10.9%)
Fracture NOS	9/55 (16.4%)
Investigations
Activated partial thromboplastin ti	3/55 (5.5%)
Blood alkaline phosphatase increase	3/55 (5.5%)
Blood bilirubin increased	4/55 (7.3%)
Blood creatinine increased	6/55 (10.9%)
Forced expiratory volume	9/55 (16.4%)
Lymphopenia	5/55 (9.1%)
Metabolic/laboratory - Other	3/55 (5.5%)
Pulmonary function test NOS decreas	5/55 (9.1%)
Weight decreased	3/55 (5.5%)
Metabolism and nutrition disorders
Hyperglycemia NOS	5/55 (9.1%)
Hypoalbuminemia	5/55 (9.1%)
Hypocalcemia	4/55 (7.3%)
Hypokalemia	3/55 (5.5%)
Hyponatremia	3/55 (5.5%)
Musculoskeletal and connective tissue disorders
Chest wall pain	9/55 (16.4%)
Muscle weakness NOS	3/55 (5.5%)
Musculoskeletal/soft tissue - Other	3/55 (5.5%)
Myalgia	3/55 (5.5%)
Nervous system disorders
Headache	4/55 (7.3%)
Peripheral sensory neuropathy	4/55 (7.3%)
Renal and urinary disorders
Renal/genitourinary - Other	3/55 (5.5%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	3/55 (5.5%)
Cough	18/55 (32.7%)
Dyspnea	30/55 (54.5%)
Hypoxia	4/55 (7.3%)
Pleural effusion	5/55 (9.1%)
Pneumonitis NOS	8/55 (14.5%)
Pulmonary/upper respiratory - Other	11/55 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.