Irinotecan And Cisplatin Research Articles

A phase II study of biweekly irinotecan and cisplatin for patients with extensive stage disease small cell lung cancer

An irinotecan and cisplatin (IP) combination is one of active regimen used in treatment of extensive stage disease (ED) small cell lung cancer (SCLC). However, a 4-week cycle of irinotecan treatment can result in significant myelosuppression and diarrhea. Therefore, the present study was conducted to evaluate the efficacy and safety of biweekly IP in patients with ED SCLC. Patients with previously untreated ED SCLC received intravenous irinotecan at a dose of 60mg/m(2) and cisplatin at a dose of 30mg/m(2) on days 1 and 15 every 4 weeks. Thirty-five patients were enrolled in this study. Three complete responses and 23 partial responses were confirmed, giving an overall response rate of 74.3%. After a median follow-up of 15.1 months, the median time to progression and overall survival were 7.7 months and 12.2 months, respectively. Grade 3/4 neutropenia occurred in seven patients and grade 3 febrile neutropenia was observed in one patient. Grade 3 diarrhea occurred in two patients. The combination chemotherapy of biweekly IP was found to be well tolerated and effective in patients with ED SCLC. Further evaluation of the combination of IP at the dose and schedule in this study is warranted in ED SCLC patients.

Phase II trial of irinotecan and cisplatin with early concurrent radiotherapy in limited‐disease small‐cell lung cancer

A Phase II trial of irinotecan and cisplatin (IP) with early concurrent radiotherapy was performed in limited-disease small-cell lung cancer (LD-SCLC) to evaluate the efficacy and toxicity. For untreated LD-SCLC patients, irinotecan (60 mg/m2, Days 1, 8, and 15) and cisplatin (40 mg/m2, Days 1 and 8) were repeated every 4 weeks for a maximum of 6 cycles. Thoracic radiotherapy of 1.8 Gy/day was begun on Day 1 of the second chemotherapy cycle, up to a total of 45 to 54 Gy. Prophylactic cranial irradiation (30 Gy in 10 fractions) was performed on patients with a complete response (CR). Thirty-three LD-SCLC patients were enrolled. The median age was 60 years and 31 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Twelve (36.4%) patients had N3 disease. The response rate was 87.9%, with a CR rate of 45.5%. At a median follow-up period of 27 months the median progression-free survival (PFS) and overall survival (OS) were 14.4 and 26.1 months, respectively, with 2-year PFS and OS rates of 26.8% and 54.9%. The dominating toxicity was neutropenia, with grade 3-5 of 81.8%. The most common grade 3-5 nonhematologic toxicities were diarrhea (21.2%), anorexia (21.2%), and fatigue (21.2%). Grade 3-5 radiation esophagitis and pneumonitis occurred in 18.2% and 9.1% of patients, respectively. There were 2 treatment-related deaths from sepsis and radiation pneumonitis. IP with early concurrent radiotherapy was effective and tolerable in untreated LD-SCLC.

Phase II Study of Etoposide and Cisplatin With Concurrent Twice-Daily Thoracic Radiotherapy Followed by Irinotecan and Cisplatin in Patients With Limited-Disease Small-Cell Lung Cancer: West Japan Thoracic Oncology Group 9902

We initially conducted a randomized phase II study to compare irinotecan and cisplatin (IP) versus irinotecan, cisplatin, and etoposide (IPE) after etoposide and cisplatin (EP) with concurrent twice-daily thoracic radiotherapy (TRT) in limited-disease small-cell lung cancer (LD-SCLC). We amended the protocol to evaluate IP after EP with concurrent twice-daily TRT in a single-arm phase II study because of an unacceptable toxicity in IPE. Previously untreated patients with LD-SCLC were treated intravenously with etoposide 100 mg/m2 on days 1 through 3 and cisplatin 80 mg/m2 on day 1 with concurrent twice-daily TRT (1.5 Gy per fraction, a total dose of 45 Gy) beginning on day 2 followed by three cycles of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 of a 4-week cycle. Of the 51 patients enrolled, 49 patients were assessable for response and toxicity. The overall response rate and complete response rate were 88% and 41%, respectively. The median survival time for all patients was 23 months. The 2-year and 3-year survival rates were 49% and 29.7%, respectively. The median progression-free survival was 11.8 months. The major toxicities observed were neutropenia (grade 4, 84%), febrile neutropenia (grade 3, 31%), infection (grade 3 to 4, 33%), electrolytes imbalance (grade 3 to 4, 20%), and diarrhea (grade 3 to 4, 14%). EP with concurrent twice-daily TRT followed by the consolidation of IP appears to be an active regimen which deserves further phase III testing in patients with LD-SCLC.

Fractionated Administration of Irinotecan and Cisplatin in Japanese Patients With Extensive-Stage–Disease Small-Cell Lung Cancer

TO THE EDITOR: We read with great interest the recent article by Hanna et al, in which they reported irinotecan and cisplatin (IP) regimen was not superior to the etoposide and cisplatin (EP) regimen for extensive-stage–disease (ED) small-cell lung cancer (SCLC), even though Noda et al clearly showed the superiority of IP regimen over EP regimen. We previously fractionated the schedule of IP to obtain the synergistic effect of the two drugs and to reduce toxicities. The recommended doses of irinotecan and cisplatin on days 1 and 8 were determined to be 50 mg/m and 60 mg/m, respectively. However, the phase II study for ED SCLC was stopped early because of poor outcomes in the interim analysis. Despite the small number of patients in our study, the median survival time and 1-year survival rates were similar to those reported in the study by Hanna et al (Table 1). The delivered doses of irinotecan and cisplatin in their study were 1.8 times and 0.7 times as much as those of our study, respectively (Table 1). In comparison to the study by Noda et al, we should have modified fractionated administration by escalating the dose of irinotecan and reducing that of cisplatin to improve the outcomes. However, both irinotecan and cisplatin in the Hanna et al study showed more dose intensity than that reported in the Noda et al study. Hanna et al suggested that IP might therefore be a better regimen for Japanese patients. We considered fractionated administrations of IP to be inferior to the original schedules of IP (cisplatin on day 1 and irinotecan on days 1, 8, and 15) for not only American but also Japanese patients with ED SCLC based on the findings of our study. Another explanation for the negative results of the Hanna et al study might be due to salvage chemotherapy. More patients on the IP arm received subsequent treatment with etoposide (47.2% v 22.6%) whereas more patients on the EP arm received subsequent treatment with topoisomerase I inhibitors including irinotecan or topotecan (33% v 24.1%). Noda et al did not describe the use of salvage chemotherapy, which might have affected the survival difference in both arms. Because chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI), followed by fluorouracil, leucovorin, and oxaliplatin (FOLFOX), had almost the same efficacy as that with FOLFOX followed by FOLFIRI in the treatment of advanced colorectal cancer, IP followed by EP might therefore have had the same efficacy as EP followed by IP in the treatment of ED SCLC. To achieve a prolonged survival, the administration of all three active cytotoxic drugs (cisplatin, irinotecan, and etoposide) during the treatment course may thus be necessary.

Irinotecan in small cell lung cancer

伊立替康单药及联合方案在小细胞肺癌(SCLC)的治疗中均显示了良好的抗瘤活性,特别是与顺铂联合在SCLC的一线治疗中较足叶乙甙加顺铂方案明显延长了患者的生存期.但其独特的毒副作用腹泻发生率较高.现对伊立替康治疗小细胞肺癌的疗效及其副作用进行综述。

Irinotecan in the treatment of small cell lung cancer: a review of patient safety considerations

A water soluble derivative of camptothecin, irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC), as well as non-SCLC and gastrointestinal cancers. This extended review of recently concluded and ongoing studies focuses on irinotecan in the treatment of limited (LD) and extensive (ED) SCLC specifically considering the safety of patients. Irinotecan-induced diarrhoea is pervasive, and can be severe and life-threatening especially in combination with neutropenia. It can have a significant impact on patient quality of life, negatively influencing compliance with therapy and dose-intensity. For LD SCLC, irinotecan can be administered with radiotherapy concurrently or sequentially. In a Phase III study for ED SCLC comparing etoposide and cisplatin (EP) and irinotecan and cisplatin (IP) regimens, severe myelosuppression was more frequent in the EP arm than in the IP arm, and conversely severe or life-threatening diarrhoea was more frequent in the IP arm than in the EP arm. IP resulted in significantly higher response rates and overall survival in Japan, and confirmatory Phase III studies are ongoing. Irinotecan should not be administered to patients with any degree of ongoing diarrhoea above their baseline. Irinotecan can be administered with relative safety for patients with SCLC only through careful patient monitoring, especially regarding diarrhoea and myelosuppression.

Randomized Phase II study of two opposite administration sequences of irinotecan and cisplatin in patients with advanced nonsmall cell lung carcinoma

Combined chemotherapy with irinotecan and cisplatin (IP) is active in patients with nonsmall cell lung carcinoma (NSCLC). However, the optimal administration schedule needs to be defined to maximize its synergic effect. The authors evaluated the efficacy, toxicity, and pharmacokinetics (PK) of IP chemotherapy given on two administration sequences in chemotherapy-naive patients with NSCLC. Eighty eligible patients were assigned randomly to receive 1 of 2 irinotecan and cisplatin administration sequences on Day 1: irinotecan followed by cisplatin (I-P) (n = 39 patients) or cisplatin followed by irinotecan (P-I) (n = 41 patients). Treatment was comprised of irinotecan at a dose of 80 mg/m(2) intravenously on Days 1 and 8 and cisplatin at a dose of 60 mg/m(2) intravenously on Day 1 of a 21-day cycle for a maximum of 6 cycles. For PK analysis, serial plasma samples were obtained on Day 1 of the first cycle. In total, 77 patients were assessable for efficacy. The overall response rate was 47%, and there was a trend in favor of P-I (54%) compared with I-P (39%). In multivariate logistic regression analysis, the P-I sequence and female gender were found to be significant predictors of a better response (P = 0.047 and P = 0.011, respectively). Overall toxicity profiles and PK parameters were similar in both arms. IP chemotherapy showed promising activity with a favorable 1-year survival rate. For future clinical use, the authors recommend administering cisplatin first and then irinotecan, because that sequence was associated with a higher response rate.

Pilot Study of Concurrent Etoposide and Cisplatin Plus Accelerated Hyperfractionated Thoracic Radiotherapy Followed by Irinotecan and Cisplatin for Limited-Stage Small Cell Lung Cancer: Japan Clinical Oncology Group 9903

Irinotecan and cisplatin (IP) significantly improved survival compared with etoposide and cisplatin (EP), in patients with extensive-stage small cell lung cancer (SCLC) in a previous Japan Clinical Oncology Group (JCOG) randomized trial. JCOG9903 was conducted to evaluate the safety of sequentially given IP following concurrent EP plus twice-daily thoracic irradiation (TRT) for the treatment of limited-stage SCLC (LSCLC). Between October 1999 and July 2000, 31 patients were accrued from 10 institutions. Thirty patients were assessable for toxicity, response, and survival. Treatment consisted of etoposide 100 mg/m(2) on days 1 to 3, cisplatin 80 mg/m(2) on day 1, and concurrent twice-daily TRT of 45 Gy beginning on day 2. The IP regimen started on day 29 and consisted of irinotecan 60 mg/m(2) on days 1, 8, and 15 and cisplatin 60 mg/m(2) on day 1, with three 28-day cycles. There were no treatment-related deaths. The response rate was 97% (complete response, 37%; partial response, 60%). Median overall survival was 20.2 months; 1-, 2-, and 3-year survival rates were 76%, 41%, and 38%, respectively. Of the 24 patients who started the IP regimen, 22 received two or more cycles. Hematologic toxicities of grade 3 or 4 included neutropenia (67%), anemia (50%), and thrombocytopenia (4%). Nonhematologic toxicities of grade 3 or 4 included diarrhea (8%), vomiting (8%), and febrile neutropenia (8%). Of the 20 patients with recurrence, none had local recurrence alone and only two had both local and distant metastasis as the initial sites of disease progression. IP following concurrent EP plus twice-daily TRT is safe with acceptable toxicities. A randomized phase III trial comparing EP with IP following EP plus concurrent TRT for LSCLC is ongoing (JCOG0202).