A dose-escalation study of irinotecan (CPT-11) in combination with cisplatin in patients with advanced non-small cell lung cancer previously treated with a docetaxel-based front line chemotherapy (original) (raw)
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Lung Cancer, 2001
Irinotecan (CPT-11) and cisplatin (P) are both active agents against non-small cell lung cancer (NSCLC), and their combination has shown in vitro an additive or synergistic effect. We conducted a phase II study to determine the toxicity and efficacy of their combination as salvage treatment in patients with advanced NSCLC progressing after a docetaxel-based front line regimen. Forty-four patients with histologically confirmed NSCLC were enrolled. The patients' median age was 60.5 years; 39 patients (87%) were male; 38 (86%) had stage IV disease; and 32 (73%) had a performance status (WHO) 0-1. CPT-11 was administered as a 60 min i.v. infusion at a dose of 100 mg/m(2) on day 1 and 110 mg/m(2) on day 8; P was administered at a dose of 80 mg/m(2) on day 8 after CPT-11 administration. Treatment was repeated every 3 weeks. A total of 159 chemotherapy cycles was administered. In an intention-to-treat analysis, nine patients (22; 95% CI: 9.28-34.62%) achieved a partial response (PR), 8 (20%) had stable disease (SD), and 24 (58%) progressive disease (PD). The median duration of response was 4 months, the median time-to-progression (TTP) 8 months, and the median survival for the entire group 8 months. Grade 3-4 neutropenia was observed in 20 (46%) patients and in four cases this was febrile, requiring patient's hospitalisation. Grade 3-4 thrombocytopenia occurred in four (9%) patients. Grade 3-4 diarrhoea was seen in 12 (27%) patients and three of them required hospitalisation. Grade 2-3 neurotoxicity was observed in two (4%) patients and grade 2-3 fatigue in 14 (32%). Other toxicity was mild and no treatment-related death was reported. The combination of CPT-11 and P is a safe, well-tolerated, and active regimen for the treatment of patients with advanced NSCLC previously treated with a docetaxel-based front-line regimen.
Weekly administration of irinotecan (CPT-11) plus cisplatin for non-small cell lung cancer
Anticancer research
Weekly administration of irinotecan plus cisplatin was evaluated for untreated patients with non-small cell lung cancer (NSCLC). Sixty mg/m(2) of irinotecan plus 30 mg/m(2) of cisplatin were administered on days 1, 8 and 15 every 4 weeks. Patients with no evidence of disease progression were treated with at least two cycles (8 weeks). Of the 39 patients, 29 were provided an antidiarrheal program consisting of sodium bicarbonate and magnesium oxide. There were 13 partial responses and an overall response rate of 33.3% [95% CI: 20%-50%]. The median time to progression and survival were 64 days and 12.8 months, respectively. Grade 4 neutropenia occurred in 15.4% of the patients, and Grade 3 and 4 diarrhea was observed in 12.8% and 2.6%, respectively. The incidence of leukopenia of grade 3-4 was significantly lower in patients provided with the antidiarrheal program due to lack of decrease in the lymphocyte count. This phase II study indicated that weekly irinotecan plus cisplatin admin...
Cancer, 2010
BACKGROUND:Irinotecan has significant activity in small-cell lung cancer (SCLC). The authors' previous phase 1 study of alternating weekly therapy with irinotecan/cisplatin (IP), etoposide/cisplatin (EP), and granulocyte–colony-stimulating factor (G-CSF) support was well tolerated and active in patients with SCLC. A phase 2 trial was conducted to estimate the efficacy of this regimen in previously untreated patients with extensive SCLC.Irinotecan has significant activity in small-cell lung cancer (SCLC). The authors' previous phase 1 study of alternating weekly therapy with irinotecan/cisplatin (IP), etoposide/cisplatin (EP), and granulocyte–colony-stimulating factor (G-CSF) support was well tolerated and active in patients with SCLC. A phase 2 trial was conducted to estimate the efficacy of this regimen in previously untreated patients with extensive SCLC.METHODS:A total of 33 patients were treated between June 2002 and July 2007. Patients received 12 weeks of therapy with cisplatin (20 mg/m2) on Day 1 and irinotecan (100 mg/m2) on Day 1 and G-CSF on Days 2 to 5 (Weeks 1, 3, 5, 7, 9, and 11) followed by cisplatin (20 mg/m2) on Day 1 and etoposide (60 mg/m2) on Days 1 to 3 with G-CSF on Days 4 to 7 (Weeks 2, 4, 6, 8, 10, and 12). The primary endpoint was 1-year survival rate.A total of 33 patients were treated between June 2002 and July 2007. Patients received 12 weeks of therapy with cisplatin (20 mg/m2) on Day 1 and irinotecan (100 mg/m2) on Day 1 and G-CSF on Days 2 to 5 (Weeks 1, 3, 5, 7, 9, and 11) followed by cisplatin (20 mg/m2) on Day 1 and etoposide (60 mg/m2) on Days 1 to 3 with G-CSF on Days 4 to 7 (Weeks 2, 4, 6, 8, 10, and 12). The primary endpoint was 1-year survival rate.RESULTS:Grade 4 neutropenia (toxicities were determined using the National Cancer Institute Common Toxicity Criteria [version 2.0]) was noted in 5 (1.5%) of 343 courses with neutropenic fever in only 5 (1%) of 343 courses. One patient died of neutropenic sepsis. Nonhematologic toxicities grade ≥2 were observed in 15 (4%) of 343 courses and were limited to fatigue, hyponatremia, and diarrhea. The overall objective response rate was 89% in 28 assessable patients (no complete responses and 25 partial responses). The median progression-free and overall survivals were 6.0 months and 10.9 months, respectively. The 1-year survival rate was 33%.Grade 4 neutropenia (toxicities were determined using the National Cancer Institute Common Toxicity Criteria [version 2.0]) was noted in 5 (1.5%) of 343 courses with neutropenic fever in only 5 (1%) of 343 courses. One patient died of neutropenic sepsis. Nonhematologic toxicities grade ≥2 were observed in 15 (4%) of 343 courses and were limited to fatigue, hyponatremia, and diarrhea. The overall objective response rate was 89% in 28 assessable patients (no complete responses and 25 partial responses). The median progression-free and overall survivals were 6.0 months and 10.9 months, respectively. The 1-year survival rate was 33%.CONCLUSIONS:Weekly therapy with IP alternating with EP and G-CSF support was well tolerated in patients with extensive SCLC, but did not demonstrate improved progression-free or overall survival when compared with historical controls at the study institution. Cancer 2010. © 2010 American Cancer Society.Weekly therapy with IP alternating with EP and G-CSF support was well tolerated in patients with extensive SCLC, but did not demonstrate improved progression-free or overall survival when compared with historical controls at the study institution. Cancer 2010. © 2010 American Cancer Society.