Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP) for non-small-cell lung cancer

Kobayashi, Kunihiko; Shinbara, A.; Kamimura, Mitsuhiro; Takeda, Yuichiro; Kudo, Kohsuke; Kabe, Junzaburo; Hibino, Suguru; Hino, Mitsunori; Shibuya, Masabumi; Kudoh, Shouji

doi:10.1007/s002800050784

Cited by 28 publications

(22 citation statements)

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“…In a phase II study of irinotecan and cisplatin in patients with stage IIIB or IV disease, the response rate was 52% and the median survival time was 52 weeks (Masuda et al, 1998). In order to develop a more effective regimen, studies have been conducted in which the dose intensity of irinotecan and/or cisplatin has been increased (Masuda et al, 1994;Kobayashi et al, 1998;Ueoka et al, 2001), and in which various triplet-drug combination therapies using irinotecan, cisplatin, and another drug have been explored (Shinkai et al, 1994). Ifosfamide is an analogue of cyclophosphamide and shows significant activity against NSCLC (Costanza et al, 1978).…”

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Phase II study of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with stage IIIb and IV non-small-cell lung cancer

Fujita¹,

Ohkubo²,

Hoshino³

et al. 2003

Br J Cancer

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A phase II study of cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony stimulating factor (rhG-CSF) support was conducted in previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). Between June 1998 and August 2001, 50 patients were registered in this phase II study. Cisplatin (20 mg m À2 ) and ifosfamide (1.5 g m À2 ) were administered on days 1 -4 and irinotecan (60 mg m À2 ) was given on days 1, 8, and 15, respectively. This regimen was repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50 mg m À2 on days 5 -18 except on the days of irinotecan treatment. In total, 49 patients were assessable for toxicity and response and 50 for survival. In all, 33, patients (67.3%; 95% confidence interval 57.4 -77.2%) achieved an objective response. The median response duration was 192 days and the median time to progression for 49 patients was 170 days. The median survival time was 540 days with 1-and 2-year survival rates of 63.5 and 30.7%, respectively. Grade 3 or 4 neutropenia and thrombocytopenia developed in 63.3 and 38.8% of the patients, respectively. In conclusion, the combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support was highly effective for the treatment of stage IIIB or IV NSCLC with acceptable toxicities. In the 1990s, a number of new chemotherapeutic agents such as the taxanes, vinorelbine, gemcitabine, and irinotecan were introduced into the management of advanced non-small-cell lung cancer (NSCLC). Irinotecan is a semisynthetic water-soluble derivative of camptothecin. Its mechanism of action is the inhibition of DNA topoisomerase I through the formation of topoisomerase I -DNA cleavable complexes (Hsiang et al, 1985;Hertzberg et al, 1989). A phase II study showed a high clinical efficacy of irinotecan in previously untreated NSCLC, with patients responding at a rate of 32% (Fukuoka et al, 1992). In a phase II study of irinotecan and cisplatin in patients with stage IIIB or IV disease, the response rate was 52% and the median survival time was 52 weeks (Masuda et al, 1998). In order to develop a more effective regimen, studies have been conducted in which the dose intensity of irinotecan and/or cisplatin has been increased (Masuda et al, 1994;Kobayashi et al, 1998;Ueoka et al, 2001), and in which various triplet-drug combination therapies using irinotecan, cisplatin, and another drug have been explored (Shinkai et al, 1994). Ifosfamide is an analogue of cyclophosphamide and shows significant activity against NSCLC (Costanza et al, 1978).In the light of these previous studies, we conducted a phase I study of escalating dose of irinotecan combined with a fixed schedule of cisplatin and ifosfamide with recombinant human granulocyte colony stimulating factor (rhG-CSF) support in advanced NSCLC (Fujita et al, 1999). The combination of cisplatin and ifosfamide at respective doses of 20 mg m À2 and 1.5 g m À2 was administered on days 1 -4, and irinotecan was given on days 1, 8, and 15, starting at 40 mg m À...

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Phase II study of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with stage IIIb and IV non-small-cell lung cancer

Fujita¹,

Ohkubo²,

Hoshino³

et al. 2003

Br J Cancer

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“…In the weekly administration of both CPT-11 and CDDP conducted by Kobayashi et al under similar consideration (Kobayashi et al, 1998), the most prominent toxicity was leukopenia, and diarrhoea was not a dose-limiting toxicity. CPT-11 has been considered as the major cause of diarrhoea in this combination.…”

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confidence: 95%

Fractionated administration of irinotecan and cisplatin for treatment of non-small-cell lung cancer: a phase II study of Okayama Lung Cancer Study Group

et al. 2001

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A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg m –2 was given first and followed by CPT-11 at a dose of 50 mg m –2 . Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32–63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities. © 2001 Cancer Research Campaign http://www.bjcancer.com

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“…It was reported that SN-38G is transformed to active SN-38 by bacterial beta-glucuronidase 18) . In reports from us and other researchers, damage in the small intestine was observed in humans 7,19) where little bacteria exist and, therefore, another key of CPT-induced diarrhea was considered.…”

Section: Discussionmentioning

confidence: 99%

Biweekly Administration of Irinotecan (Cpt-11) Plus Cisplatin With an Antidiarrheal Program of Intestinal Alkalization to Reduce Diarrhea in Cancer Patients

Kobayashi

Sakuyama

Koizumi

et al. 2012

Ann. Cancer Res. Therap.

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Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP) for non-small-cell lung cancer

Abstract: The value of weekly administration of CDDP in combination with CPT-11 was shown by (1) diarrhea not being dose-limiting, (2) mild nausea, (3) well-maintained AUC of free platinum, and (4) promising activity.

Cited by 28 publications

References 7 publications

Phase II study of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with stage IIIb and IV non-small-cell lung cancer

Phase II study of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with stage IIIb and IV non-small-cell lung cancer

Fractionated administration of irinotecan and cisplatin for treatment of non-small-cell lung cancer: a phase II study of Okayama Lung Cancer Study Group

Biweekly Administration of Irinotecan (Cpt-11) Plus Cisplatin With an Antidiarrheal Program of Intestinal Alkalization to Reduce Diarrhea in Cancer Patients

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