A randomized phase III trial of irinotecan plus carboplatin versus etoposide plus carboplatin in patients with small cell lung cancer, extensive disease (SCLC-ED): IRIS-Study

7523 Background: A Japanese randomized trial has shown superior survival for SCLC-ED patients receiving irinotecan+cisplatin as compared to etoposide+cisplatin. Our trial was performed to evaluate the effect of irinotecan+carboplatin compared to oral etoposide+carboplatin. Patients and Methods: In a phase III trial, patients with SCLC-ED were randomly assigned to receive carboplatin, AUC=4 (Chatelut formula) and irinotecan, 175 mg/m2, both on day 1 (IC) or carboplatin (Chatelut AUC=4) on day 1 and etoposide 120 mg/m2/day, orally, on days 1–5 (EC). In both arms, courses were repeated on day 21 with 4 cycles planned. Primary endpoint was overall survival (OS), secondary endpoints were quality of life, evaluated by EORTC-QLQ-C30 and QLQ-LC 13, and complete response rate. There were neither upper limits for age or performance status. Results: Between November, 2001 and July, 2005, 220 patients were randomized. 210 patients were eligible for analysis (other type of cancer, 8 pts., limited disease, 1 pt., elevated liver function tests, 1 pt.). Performance status (PS) 0: 20 patients, PS 1: 91, PS 2: 62, PS 3: 29, PS 4: 8. Median age IC was 67 years (46–81), EC 67 years (39–82). OS was 255 days (IC) versus 214 days (EC) (P=0.04, log rank test). HR for overall survival was 1.34, 95% CI: 1.01–1.79. 1-year survival was 35% vs 28%. CR was observed in 18 patients in the IC arm and 7 patients in the EC arm (P=0.02, chi-square test). There were no statistically significant differences with respect to haematological grade III-IV toxicity. No severe diarrhea was observed in the IC group. There were no significant differences regarding quality of life. Conclusion: Irinotecan + carboplatin is superior to oral etoposide + carboplatin with respect to overall survival in SCLC-ED. No significant financial relationships to disclose.

Download Full-text

Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting Induced by Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Trial (CLOG1302 study)

Journal of Clinical Oncology ◽

10.1200/jco.2017.72.2538 ◽

2017 ◽

Vol 35 (31) ◽

pp. 3558-3565 ◽

Cited By ~ 10

Author(s):

Lingyun Zhang ◽

Xiujuan Qu ◽

Yuee Teng ◽

Jing Shi ◽

Ping Yu ◽

...

Keyword(s):

Quality Of Life ◽

Complete Response ◽

Emetogenic Chemotherapy ◽

Nausea And Vomiting ◽

Phase Iii ◽

Highly Emetogenic Chemotherapy ◽

Double Blind ◽

Phase Iii Trial ◽

Delayed Nausea

Purpose We examined the efficacy and safety of thalidomide (THD) for the prevention of delayed nausea and vomiting in patients who received highly emetogenic chemotherapy (HEC). Patients and Methods In a randomized, double-blind, active-controlled, phase III trial, chemotherapy-naive patients with cancer who were scheduled to receive HEC that contained cisplatin or cyclophosphamide-doxorubicin/epirubincin ≥ 50 mg/m2 regimens were randomly assigned to a THD group (100 mg twice daily on days 1 to 5) or placebo group, both with palonosetron (0.25 mg on day 1) and dexamethasone (12 mg on day 1; 8 mg on days 2 to 4). Primary end point was complete response to vomiting—no emesis or use of rescue medication—in the delayed phase (25 to 120 h). Nausea and anorexia on days 1 to 5 were evaluated by the 4-point Likert scale (0, no symptoms; 3, severe). Quality of life was assessed by the European Organization for Research and Treatment of Cancer QLQ-C30 version 3 questionnaire on days −1 and 6. Results Of 656 patients, 638 were evaluable: 317 in the THD group and 321 in the control group. Compared with placebo, delayed and overall (0 to 120 h) complete response rates to vomiting were significantly higher with THD: 76.9% versus 61.7% ( P < .001) and 66.1% versus 53.3% ( P = .001), respectively. Rates of no nausea were also higher in the THD group (delayed: 47.3% v 33.3%; P < .001; overall: 41% v 29.6%; P = .003), and mean scores of anorexia were lower overall (0.44 ± 0.717 v 0.64 ± 0.844; P = .003). Adverse effects were mild to moderate. The THD group had increased sedation, dizziness, constipation, and dry mouth, but experienced better quality of life after chemotherapy. Conclusion Thalidomide combined with palonosetron and dexamethasone significantly improved HEC-induced delayed nausea and vomiting prevention in chemotherapy-naive patients.

Download Full-text

Topotecan Versus Observation After Cisplatin Plus Etoposide in Extensive-Stage Small-Cell Lung Cancer: E7593—A Phase III Trial of the Eastern Cooperative Oncology Group

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.8.2114 ◽

2001 ◽

Vol 19 (8) ◽

pp. 2114-2122 ◽

Cited By ~ 204

Author(s):

Joan H. Schiller ◽

Sudeshna Adak ◽

David Cella ◽

Russell F. DeVore ◽

David H. Johnson

Keyword(s):

Quality Of Life ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Small Cell ◽

Phase Iii ◽

Oncology Group ◽

Small Cell Lung ◽

Phase Iii Trial ◽

Extensive Stage

PURPOSE: To determine the efficacy of topotecan in combination with standard chemotherapy in previously untreated patients with extensive-stage small-cell lung cancer (SCLC), the Eastern Cooperative Oncology Group (ECOG) conducted a phase III trial. PATIENTS AND METHODS: Eligible patients had measurable or assessable disease and an ECOG performance status of 0 to 2; stable brain metastases were allowed. All patients received four cycles of cisplatin and etoposide every 3 weeks (step 1; PE). Patients with stable or responding disease were then randomized to observation or four cycles of topotecan (1.5 mg/m2/d for 5 days, every 3 weeks; step 2). A total of 402 eligible patients were registered to step 1, and 223 eligible patients were registered to step 2 (observation, n = 111; topotecan, n = 112). RESULTS: Complete and partial response rates to induction PE were 3% and 32%, respectively. A 7% response rate was observed with topotecan (complete response, 2%; partial response, 5%). The median survival time for all 402 eligible patients was 9.6 months. Progression-free survival (PFS) from date of randomization on step 2 was significantly better with topotecan compared with observation (3.6 months v 2.3 months; P < .001). However, overall survival from date of randomization on step 2 was not significantly different between the observation and topotecan arms (8.9 months v 9.3 months; P = .43). Grade 4 neutropenia and thrombocytopenia occurred in 50% and 3%, respectively, of PE patients in step 1 and 60% and 13% of topotecan patients in step 2. Grade 4/5 infection was observed in 4.6% of PE patients and 1.8% of topotecan patients. Grade 3/4 anemia developed in 22% of patients who received topotecan. No difference in quality of life between topotecan and observation was observed at any assessment time or for any of the subscale scores. CONCLUSION: Four cycles of PE induction therapy followed by four cycles of topotecan improved PFS but failed to improve overall survival or quality of life in extensive-stage SCLC. Four cycles of standard PE remains an appropriate first-line treatment for extensive-stage SCLC patients with good performance status.

Download Full-text

COUGAR-02: A randomized phase III study of docetaxel versus active symptom control in advanced esophagogastric adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.lba4 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. LBA4-LBA4 ◽

Cited By ~ 9

Author(s):

Hugo Ford ◽

Andrea Marshall ◽

Jonathan Wadsley ◽

Fareeda Y. Coxon ◽

Wasat Mansoor ◽

...

Keyword(s):

Quality Of Life ◽

Overall Survival ◽

Performance Status ◽

Symptom Control ◽

Locally Advanced ◽

Phase Iii ◽

First Line ◽

Line Chemotherapy ◽

Esophagogastric Adenocarcinoma

LBA4 Background: Survival in patients who relapse after first-line chemotherapy for advanced esophagogastric adenocarcinoma (OGC) is poor though recently randomized trials have suggested a small survival benefit for second-line chemotherapy with taxanes or irinotecan. There is very little data on quality of life or survival, particularly in patients who progress shortly after first-line therapy. Methods: COUGAR-02 was a multicenter open-label, randomized controlled phase III trial for patients with locally advanced or metastatic OGC of performance status (PS) 0-2 who had progressed within 6 months of previous platinum/fluoropyrimidine (PF) chemotherapy (CT). Patients were randomized (1:1) to receive either docetaxel 75mg/m2every 3 weeks for up to 6 cycles or active symptom control (ASC), which could include any treatment thought by the treating clinician to be appropriate for the management of symptoms including radiotherapy, steroids and supportive medications. The primary endpoint was overall survival. Secondary endpoints were response rate, toxicity, health related quality of life (HRQL) and healthcare resource use. Results: Between April 2008 and April 2012, 168 patients were recruited (84 patients in each arm). Median age was 65 years (range 28-84), 81% were male. PS at randomisation was 0 for 27%, 1 for 57% and 2 for 15%. Site of disease was stomach in 46%, esophagogastric junction in 34% and esophagus in 20%. 86% had metastatic disease. 43% progressed during previous CT, 28% progressed within 3 months of end of previous CT and 29% progressed between 3 and 6 months. 19 (23%) patients completed 6 CT cycles (median 3 cycles per patient). The main reasons for not completing treatment were progression and toxicity. Docetaxel significantly improved overall survival over ASC alone (median 5.2 months (95% CI 4.1-5.9 months) for docetaxel; 3.6 months (95% CI 3.3-4.4 months) for ASC, HR=0.67 (95% CI 0.49-0.92); p=0.01). 7% had a partial response and 46% had stable disease after CT. 21% on docetaxel had grade 4 toxicity. Conclusions: The addition of docetaxel to ASC significantly improved overall survival. Docetaxel can be considered a standard of care in this setting. Clinical trial information: 13366390.

Download Full-text