Trial Outcomes & Findings for Captopril in Treating Patients With Non-Small Cell Lung Cancer or Limited-Stage Small Cell Lung Cancer That Has Been Previously Treated With Radiation Therapy With or Without Chemotherapy (NCT NCT00077064)

Last Updated: 2018-03-08

Results Overview

Incidence of Grade 2+ radiation-induced pulmonary toxicity within 1 year after completion of radiation. Assuming that the incidence of pulmonary toxicity would be 50%, based on Fisher's exact test with a one-sided significance level of 0.05,168 randomized patients would be required to have 80% statistical power to detect a 40% relative reduction (from 50% to 30%) in the incidence of pulmonary toxicity while receiving captopril. Assuming that 15% of cases would not continue to the randomization stage and 5% of patients would be found ineligible, the target sample size was 205 patients. Given the actual sample size, power would be 25% and therefore p-values were not reported.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

81 participants

Primary outcome timeframe

Once all patients have been followed for at least 12 months

Results posted on

2018-03-08

Participant Flow

Patients were registered within 7 days prior to start of radiation therapy(RT) or during RT up to 48 hours prior completion of RT. They were randomized to captopril or observation within 48 hours prior to completion of RT. Eighty-one patients were registered, 48 did not continue to treatment assignment, 33 were randomized.

Participant milestones

Participant milestones
Measure	Clinical Observation Clinical observation	Captopril Captopril: 50 mg t.i.d.
Overall Study STARTED	17	16
Overall Study COMPLETED	17	10
Overall Study NOT COMPLETED	0	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Clinical Observation Clinical observation	Captopril Captopril: 50 mg t.i.d.
Overall Study Adverse Event	0	4
Overall Study Patient refusal	0	2

Baseline Characteristics

Captopril in Treating Patients With Non-Small Cell Lung Cancer or Limited-Stage Small Cell Lung Cancer That Has Been Previously Treated With Radiation Therapy With or Without Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Observation n=17 Participants Clinical observation	Captopril n=10 Participants Captopril: 50 mg t.i.d.	Total n=27 Participants Total of all reporting groups
Age, Continuous	67 years n=5 Participants	64 years n=7 Participants	65 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Once all patients have been followed for at least 12 months

Population: Randomized eligible patients who started study drug treatment and were followed for one year after completion of radiation treatment or experienced radiation-induced pulmonary toxicity.

Outcome measures

Outcome measures
Measure	Observation n=13 Participants Clinical observation	Captopril n=7 Participants Captopril: 50 mg t.i.d.
Incidence of Therapy-induced Lung Toxicity	23 percentage of participants Interval 11.0 to 35.0	14 percentage of participants Interval 4.0 to 24.0

SECONDARY outcome

Timeframe: Once all patients have been followed for at least 12 months

Biomarker data will not be generated from these tissue specimens, therefore this analysis will not take place.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 18 months post treatment

Population: Eligible patients with late effect and baseline and 12-month EORTC data

Only 2 patients have the required data- only 1.2% of the planned enrollment and 2.5% of the actual enrollment- which is extremely problematic as this data cannot be generalized, leads to selection bias, and is not representative of the patient population. Therefore the analysis was not conducted.

Outcome measures

Outcome measures
Measure	Observation n=2 Participants Clinical observation	Captopril Captopril: 50 mg t.i.d.
Correlation of Quality of Life With Late Effects as Measured by European Organization for Research and Treatment of Cancer (EORTC) C-30 or EORTC Lung Cancer Module (LC-13)	NA Participants Insufficient number of participants with data collected to derive a correlation	—

SECONDARY outcome

Timeframe: 2 years from completion of study treatment

Population: Randomized patients who received study drug treatment and experienced lung toxicity at 1 year

Patients who experienced a Grade 2+ radiation-induced pulmonary toxicity within 1 year after completion of radiation were assessed to determine if the toxicity persisted for 2 years.

Outcome measures

Outcome measures
Measure	Observation n=3 Participants Clinical observation	Captopril n=1 Participants Captopril: 50 mg t.i.d.
Persistence of Pulmonary Toxicity at 2 Years After Completion of Study Treatment	0 Participants	0 Participants

Adverse Events

Clinical Observation

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

Captopril

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Clinical Observation n=17 participants at risk Clinical observation	Captopril n=10 participants at risk Captopril: 50 mg t.i.d.
Cardiac disorders Cardiac General - Other:	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Dysphagia	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	20.0% 2/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Esophageal pain	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Esophageal stenosis acquired	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Nausea	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Oseophagitis NOS	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
General disorders Chest pain	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
General disorders Death NOS	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
General disorders Disease progression NOS	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Infections and infestations Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Urinary tract NOS	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Injury, poisoning and procedural complications Vessel injury-vein: SVC	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Lymphopenia	11.8% 2/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Dehydration	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Hyperglycaemia NOS	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Hypokalemia	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Musculoskeletal and connective tissue disorders Back pain	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Musculoskeletal and connective tissue disorders Muscle weakness NOS	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Nervous system disorders Peripheral sensory neuropathy	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Nervous system disorders Syncope	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	20.0% 2/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Psychiatric disorders Depression	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Cough	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	20.0% 2/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.8% 2/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	20.0% 2/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Hypoxia	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Pleural effusion	11.8% 2/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Pneumothorax NOS	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Pulmonary/upper respiratory - Other:	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Vascular disorders Hypotension NOS	0.00% 0/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Vascular disorders Thrombosis	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).

Measure	Clinical Observation n=17 participants at risk Clinical observation	Captopril n=10 participants at risk Captopril: 50 mg t.i.d.
Cardiac disorders Atrial fibrillation	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Cardiac disorders Palpitations	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Cardiac disorders Sinus tachycardia	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Eye disorders Vision blurred	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Abdominal pain NOS	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Constipation	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Dysphagia	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	20.0% 2/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Oseophagitis NOS	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Salivary gland disorder NOS	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
General disorders Fatigue	29.4% 5/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	60.0% 6/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Infections and infestations Infection - Other:	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Injury, poisoning and procedural complications Dermatitis radiation NOS	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Alanine aminotransferase increased	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Metabolic/laboratory - Other:	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Anorexia	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Hyperkalaemia	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Hypoalbuminemia	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Nervous system disorders Dizziness	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	30.0% 3/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Nervous system disorders Headache	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	20.0% 2/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Nervous system disorders Peripheral sensory neuropathy	23.5% 4/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Cough	17.6% 3/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	40.0% 4/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.6% 3/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	40.0% 4/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Pleural effusion	11.8% 2/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	11.8% 2/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Skin and subcutaneous tissue disorders Alopecia	11.8% 2/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Skin and subcutaneous tissue disorders Skin fibrosis	5.9% 1/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Skin and subcutaneous tissue disorders Skin hyperpigmentation	11.8% 2/17 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	10.0% 1/10 Adverse events reported for all eligible randomized patients who were randomized to captopril or observation. Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).