Lung Cancer
Conditions
Keywords
extensive stage small cell lung cancer
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether cisplatin combined with irinotecan is more effective than cisplatin combined with etoposide in treating extensive-stage small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin combined with either irinotecan or etoposide in treating patients who have extensive-stage small cell lung cancer.
Detailed description
OBJECTIVES: * Compare the survival of patients with extensive stage small cell lung cancer treated with cisplatin and irinotecan vs cisplatin and etoposide. * Compare the objective response rate and progression-free survival of patients treated with these regimens. * Compare the toxic effects of these regimens in these patients. * Determine the association between UGT1A1 polymorphisms and irinotecan-associated toxic effects in these patients. * Determine the association between ERCC-1 and XRCC-1 polymorphisms and non-response of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of metastatic sites (single vs multiple), lactic dehydrogenase (no greater than upper limit of normal (ULN) vs greater than ULN), and weight loss in the past 6 months (5% or less vs more than 5%). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive irinotecan IV over 90 minutes on days 1, 8, and 15 and cisplatin IV over 30-60 minutes on day 1. Courses repeat every 4 weeks. * Arm II: Patients receive etoposide IV over 30-60 minutes on days 1-3 and cisplatin IV over 30-60 minutes on day 1. Courses repeat every 3 weeks. Treatment in both arms continues for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 620 patients (310 per treatment arm) will be accrued for this study within 4 years.
Interventions
DRUGcisplatin
Arm 1: 60 mg/m2 IV (over 30-60 min) on Day 1, Q 4 weeks x 4 Cycles Arm 2: 80 mg/m2 IV (over 30-60 min) on Day 1, Q 4 weeks x 4 Cycles
DRUGetoposide
100 mg/m2 IV (over 30-60 min) on Days 1 , 2 & 3. Q 3 weeks x 4 Cycles
DRUGirinotecan hydrochloride
60 mg/m2 IV (over 90 min)on Days 1, 8 & 15. Q 4 weeks x 4 Cycles
Sponsors
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Cancer and Leukemia Group B
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed extensive stage small cell lung cancer (SCLC) * Measurable or evaluable disease by CT scan, MRI, x-ray, physical exam, or nuclear exam * Brain metastases allowed if previously treated with radiotherapy and/or surgery and are neurologically stable (i.e., no progressing symptoms and off steroids and anticonvulsants) PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-1 Life expectancy * Not specified Hematopoietic * WBC at least 3,000/mm\^3 * Absolute granulocyte count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * AST or ALT no greater than 2.5 times ULN Renal * Creatinine normal * Creatinine clearance at least 50 mL/min Other * Not pregnant or nursing * Fertile patients must use effective contraception * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * HIV negative * No concurrent AIDS-related illness PRIOR CONCURRENT THERAPY: Biologic therapy * No prior biologic therapy for SCLC * No filgrastim (G-CSF) within 24 hours of chemotherapy Chemotherapy * No prior systemic chemotherapy for SCLC Endocrine therapy * See Disease Characteristics Radiotherapy * See Disease Characteristics * At least 21 days since prior brain radiotherapy and recovered * No other prior radiotherapy for SCLC Surgery * See Disease Characteristics * At least 21 days since prior thoracic or other major surgery and recovered Other * No concurrent enzyme inducing antiepileptic drugs (phenytoin, phenobarbital, oxcarboxepine, or carbamazepine)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Weekly while on treatment, then every 3 months for first year, then every 6 months unitl a maximum of 3 years from enrollment. | Overall survival was defined as the duration between the date of randomization( enrollment) and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Every 6 weeks until disease progression or a maximum of 3 years from the date of enrollment. | Progression-Free Survival was defined as the duration from the date of randomization (enrollment) until the date of documentation of progression as defined by RECIST (a 20% increase over nadir in the sum of longest diameters of target lesions, clear progression of a non-target lesion in the opinion of the treating investigator, appearance of new lesions, or symptomatic deterioration) or death due to any cause. Patients last known to be alive and without evidence of progression were censored at the date of last contact. |
| Confirmed and Unconfirmed Complete and Partial Responses. | Every 6 weeks while on protocol treatment for a maximum of 12 weeks | Patients underwent chest CT/MRI every 6 weeks while on treatment and tumor response was evaluated by RECIST in the subset of patients with at least one target lesion at baseline. A target lesion was defined as a lesion with a longest diameter of at least 2 cm ( or at least 1 cm if by spiral CT). A complete response (CR) was defined as the disappearance of all disease, including non-target lesions. A partial response (PR) was defined as a 30% or greater decrease in the sum of the longest diameters. Confirmation of a CR or PR was defined as a second determination of CR or PR at least 4 weeks after the first determination. |
| Number of Patients With a Given Type and Grade of Adverse Event. | Every 4 weeks while subject on protocol treatment for a maximum of 12 weeks. | Only adverse events that are possibly, probably or definitely related to study drug are reported. Only patients who received protocol treatment and were assessed for adverse events are included. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cisplatin + Irinotecan | 324 |
| Cisplatin + Etoposide | 327 |
| Total | 651 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 55 | 50 |
| Overall Study | Death | 10 | 10 |
| Overall Study | Ineligible | 12 | 8 |
| Overall Study | Lack of Efficacy | 32 | 29 |
| Overall Study | Not treated | 7 | 2 |
| Overall Study | Other | 21 | 16 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Cisplatin + Etoposide | Total | Cisplatin + Irinotecan |
|---|---|---|---|
| Age, Continuous | 63 years | 62 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 14 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 288 Participants | 577 Participants | 289 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 32 Participants | 60 Participants | 28 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 particpants | 2 particpants | 2 particpants |
| Race/Ethnicity, Customized Asian | 1 particpants | 5 particpants | 4 particpants |
| Race/Ethnicity, Customized Black or African American | 18 particpants | 32 particpants | 14 particpants |
| Race/Ethnicity, Customized More than one race | 0 particpants | 2 particpants | 2 particpants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 particpants | 0 particpants | 0 particpants |
| Race/Ethnicity, Customized Unknown or Not Reported | 4 particpants | 6 particpants | 2 particpants |
| Race/Ethnicity, Customized White | 304 particpants | 604 particpants | 300 particpants |
| Sex: Female, Male Female | 145 Participants | 281 Participants | 136 Participants |
| Sex: Female, Male Male | 182 Participants | 370 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 314 / 321 | 317 / 327 |
| serious Total, serious adverse events | 107 / 321 | 31 / 327 |
Outcome results
Primary
Overall Survival
Overall survival was defined as the duration between the date of randomization( enrollment) and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.
Time frame: Weekly while on treatment, then every 3 months for first year, then every 6 months unitl a maximum of 3 years from enrollment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cisplatin + Irinotecan | Overall Survival | 9.9 Months |
| Cisplatin + Etoposide | Overall Survival | 9.1 Months |
Secondary
Confirmed and Unconfirmed Complete and Partial Responses.
Patients underwent chest CT/MRI every 6 weeks while on treatment and tumor response was evaluated by RECIST in the subset of patients with at least one target lesion at baseline. A target lesion was defined as a lesion with a longest diameter of at least 2 cm ( or at least 1 cm if by spiral CT). A complete response (CR) was defined as the disappearance of all disease, including non-target lesions. A partial response (PR) was defined as a 30% or greater decrease in the sum of the longest diameters. Confirmation of a CR or PR was defined as a second determination of CR or PR at least 4 weeks after the first determination.
Time frame: Every 6 weeks while on protocol treatment for a maximum of 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cisplatin + Irinotecan | Confirmed and Unconfirmed Complete and Partial Responses. | 197 participants |
| Cisplatin + Etoposide | Confirmed and Unconfirmed Complete and Partial Responses. | 190 participants |
Secondary
Number of Patients With a Given Type and Grade of Adverse Event.
Only adverse events that are possibly, probably or definitely related to study drug are reported. Only patients who received protocol treatment and were assessed for adverse events are included.
Time frame: Every 4 weeks while subject on protocol treatment for a maximum of 12 weeks.
Population: Eligible patients who received protocol treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypophosphatemia | 7 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Cardiac ischemia/infarction | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypotension | 14 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Edema | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypoxia | 7 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Abdominal pain/cramping | 8 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Ileus | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Epistaxis | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Infection w/o 3-4 neutropenia | 12 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Cardiovascular-other | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Infection with 3-4 neutropenia | 20 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Erythema multiforme/blistering | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Infection, unk ANC | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Apnea | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Inner ear-hearing loss | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Esophagitis/dysphagia | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Insomnia | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Cataract | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Joint,muscle,bone-other | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Fatigue/malaise/lethargy | 45 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | LVEF decrease/CHF | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Anal incontinence | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Leukopenia | 57 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Febrile neutropenia | 11 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Lipase increase | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Cerebrovascular ischemia | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Lung-other | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Fever without neutropenia | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Lymphopenia | 8 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Arrhythmia, NOS | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Melena/ GI bleeding | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Flu-like symptoms-other | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Metabolic-other | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Chest pain,not cardio or pleur | 4 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Mood/consciousness change, NOS | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | GGT increase | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Muscle weakness (not neuro) | 4 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Alkaline phosphatase increase | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Myalgia | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | GI Mucositis, NOS | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Nausea | 46 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Colitis | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Neuro-other | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | GI-other | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Neutropenia/granulocytopenia | 108 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Arthralgia | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | PRBC transfusion | 36 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | GU-other | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Pain-other | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Confusion | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Personality/behavioral change | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Gastric ulcer | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Platelet transfusion | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Anemia | 19 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Pneumonitis/infiltrates | 4 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Gastritis | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Pneumothorax | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Constipation/bowel obstruction | 4 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Prothrombin time increase | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Headache | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Pruritus | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Ataxia (incoordination) | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | RT-pain | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hematemesis | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Rash/desquamation | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Creatinine increase | 9 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Renal failure | 4 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hematologic-other | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Reportable adverse event, NOS | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Acidosis | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Respiratory infect w/ neutrop | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hemorrhage-other | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Respiratory infect w/o neutrop | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Dehydration | 54 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Respiratory infection, unk ANC | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hyperglycemia | 12 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | SGOT (AST) increase | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Bilirubin increase | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | SGPT (ALT) increase | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hyperkalemia | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | SIADH | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Delusions | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Second primary | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypermagnesemia | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Seizures | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Anorexia | 36 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Sensory neuropathy | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypernatremia | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Sinus tachycardia | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Depression | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Somnolence/consciousness loss | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypertension | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Stomatitis/pharyngitis | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Blurred vision | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Supraventricular arrhythmia | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hyperuricemia | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Syncope | 5 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Diarrhea without colostomy | 61 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Thrombocytopenia | 13 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypoalbuminemia | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Thrombosis/embolism | 8 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Allergic reaction | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Thrombotic microangiopathy | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypocalcemia | 6 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Tumor lysis syndrome | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Dizziness/light headedness | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Ureteral obstruction | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypoglycemia | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Urinary electrolyte wasting | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Bone pain | 8 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Urinary retention | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypokalemia | 19 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Urinary tr infect w/ neutrop | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Dyspepsia/heartburn | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Ventricular arrhythmia | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hypomagnesemia | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Voice change/stridor/larynx | 2 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Anxiety/agitation | 0 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Vomiting | 34 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Hyponatremia | 38 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Weakness (motor neuropathy) | 1 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Dyspnea | 27 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | Weight loss | 3 Participants |
| Cisplatin + Irinotecan | Number of Patients With a Given Type and Grade of Adverse Event. | ARDS | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Weight loss | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | ARDS | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Abdominal pain/cramping | 8 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Acidosis | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Alkaline phosphatase increase | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Allergic reaction | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Anal incontinence | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Anemia | 40 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Anorexia | 17 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Anxiety/agitation | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Apnea | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Arrhythmia, NOS | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Arthralgia | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Ataxia (incoordination) | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Bilirubin increase | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Blurred vision | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Bone pain | 6 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Cardiac ischemia/infarction | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Cardiovascular-other | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Cataract | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Cerebrovascular ischemia | 7 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Chest pain,not cardio or pleur | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Colitis | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Confusion | 4 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Constipation/bowel obstruction | 4 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Creatinine increase | 7 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Dehydration | 27 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Delusions | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Depression | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Diarrhea without colostomy | 9 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Dizziness/light headedness | 4 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Dyspepsia/heartburn | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Dyspnea | 21 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Edema | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Epistaxis | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Erythema multiforme/blistering | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Esophagitis/dysphagia | 3 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Fatigue/malaise/lethargy | 35 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Febrile neutropenia | 33 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Fever without neutropenia | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Flu-like symptoms-other | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | GGT increase | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | GI Mucositis, NOS | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | GI-other | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | GU-other | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Gastric ulcer | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Gastritis | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Headache | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hematemesis | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hematologic-other | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hemorrhage-other | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hyperglycemia | 17 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hyperkalemia | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypermagnesemia | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypernatremia | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypertension | 4 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hyperuricemia | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypoalbuminemia | 7 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypocalcemia | 8 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypoglycemia | 3 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypokalemia | 21 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypomagnesemia | 7 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hyponatremia | 28 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypophosphatemia | 5 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypotension | 8 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Hypoxia | 6 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Ileus | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Infection w/o 3-4 neutropenia | 13 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Infection with 3-4 neutropenia | 24 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Infection, unk ANC | 3 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Inner ear-hearing loss | 4 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Insomnia | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Joint,muscle,bone-other | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | LVEF decrease/CHF | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Leukopenia | 109 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Lipase increase | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Lung-other | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Lymphopenia | 9 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Melena/ GI bleeding | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Metabolic-other | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Mood/consciousness change, NOS | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Muscle weakness (not neuro) | 3 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Myalgia | 3 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Nausea | 35 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Neuro-other | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Neutropenia/granulocytopenia | 224 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | PRBC transfusion | 62 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Pain-other | 7 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Personality/behavioral change | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Platelet transfusion | 13 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Pneumonitis/infiltrates | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Pneumothorax | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Prothrombin time increase | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Pruritus | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | RT-pain | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Rash/desquamation | 3 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Renal failure | 7 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Reportable adverse event, NOS | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Respiratory infect w/ neutrop | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Respiratory infect w/o neutrop | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Respiratory infection, unk ANC | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | SGOT (AST) increase | 4 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | SGPT (ALT) increase | 3 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | SIADH | 3 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Second primary | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Seizures | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Sensory neuropathy | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Sinus tachycardia | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Somnolence/consciousness loss | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Stomatitis/pharyngitis | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Supraventricular arrhythmia | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Syncope | 7 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Thrombocytopenia | 52 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Thrombosis/embolism | 15 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Thrombotic microangiopathy | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Tumor lysis syndrome | 2 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Ureteral obstruction | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Urinary electrolyte wasting | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Urinary retention | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Urinary tr infect w/ neutrop | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Ventricular arrhythmia | 1 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Voice change/stridor/larynx | 0 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Vomiting | 30 Participants |
| Cisplatin + Etoposide | Number of Patients With a Given Type and Grade of Adverse Event. | Weakness (motor neuropathy) | 0 Participants |
Secondary
Progression-free Survival
Progression-Free Survival was defined as the duration from the date of randomization (enrollment) until the date of documentation of progression as defined by RECIST (a 20% increase over nadir in the sum of longest diameters of target lesions, clear progression of a non-target lesion in the opinion of the treating investigator, appearance of new lesions, or symptomatic deterioration) or death due to any cause. Patients last known to be alive and without evidence of progression were censored at the date of last contact.
Time frame: Every 6 weeks until disease progression or a maximum of 3 years from the date of enrollment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cisplatin + Irinotecan | Progression-free Survival | 5.7 months |
| Cisplatin + Etoposide | Progression-free Survival | 5.2 months |