A novel combination of cisplatin, irinotecan, and capecitabine in patients with advanced cancer

Michael Jefford, Michael Michael, Mark A. Rosenthal, Ian D. Davis, Michael Green, Bev McClure, Jennifer Smith, Brigid Waite, John Zalcberg

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Abstract

Background: We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen. Patients and methods: Intravenous cisplatin and irinotecan were to be administered on days 1 and 8, and oral capecitabine on days 1-14 of a 3-week cycle. The study was conducted in three parts. Part A: escalating doses of irinotecan (40 → 80 mg/m2) and capecitabine (1000 → 3300 mg/d) combined with a fixed dose of cisplatin (30 mg/m2). Part B: escalating doses of irinotecan (MTD-A → MTD-A + 40 mg/m2) with fixed doses of cisplatin (20 mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300 mg/d → 2600 mg/d) with fixed doses of cisplatin (20 mg/m2) and irinotecan (60 mg/m 2). Results: Of 51 eligible patients 27 (53%) were male, median age was 58 years and 88% had PS 0-1. Major primary disease sites were colorectal (24%), unknown (14%), stomach (14%), and pancreas (12%). MTD-A was cisplatin 30 mg/m2, irinotecan 60 mg/m2, capecitabine 1000 mg/d and MTD-B was cisplatin 20 mg/m2, irinotecan 90 mg/m2, capecitabine 1000 mg/d. An MTD was not formally established for part C. DLTs consisted of infection with neutropenia (1), diarrhea and fatigue (1), hypokalemia (1), diarrhea and febrile neutropenia (1) and C2 delay of ≥2 weeks or 25% dose reduction in C1 due to neutropenia or thrombocytopenia (6). Seven patients had a partial response to treatment (four colorectal, one SCLC, one NSCLC, one unknown primary), twenty seven SD (53%), twelve PD (24%) and five NE (10%). Conclusion: CIC was associated with moderate toxicity and only modest antitumor activity. We conclude that this regimen has insufficient activity to justify further study in the phase II setting.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalInvestigational New Drugs
Volume22
Issue number2
DOIs
Publication statusPublished - 1 Apr 2004

Keywords

  • Capecitabine
  • Cisplatin
  • Clinical trials
  • Irinotecan
  • Phase I

Cite this

Jefford, Michael ; Michael, Michael ; Rosenthal, Mark A. ; Davis, Ian D. ; Green, Michael ; McClure, Bev ; Smith, Jennifer ; Waite, Brigid ; Zalcberg, John. / A novel combination of cisplatin, irinotecan, and capecitabine in patients with advanced cancer. In: Investigational New Drugs. 2004 ; Vol. 22, No. 2. pp. 185-192.
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title = "A novel combination of cisplatin, irinotecan, and capecitabine in patients with advanced cancer",
abstract = "Background: We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen. Patients and methods: Intravenous cisplatin and irinotecan were to be administered on days 1 and 8, and oral capecitabine on days 1-14 of a 3-week cycle. The study was conducted in three parts. Part A: escalating doses of irinotecan (40 → 80 mg/m2) and capecitabine (1000 → 3300 mg/d) combined with a fixed dose of cisplatin (30 mg/m2). Part B: escalating doses of irinotecan (MTD-A → MTD-A + 40 mg/m2) with fixed doses of cisplatin (20 mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300 mg/d → 2600 mg/d) with fixed doses of cisplatin (20 mg/m2) and irinotecan (60 mg/m 2). Results: Of 51 eligible patients 27 (53{\%}) were male, median age was 58 years and 88{\%} had PS 0-1. Major primary disease sites were colorectal (24{\%}), unknown (14{\%}), stomach (14{\%}), and pancreas (12{\%}). MTD-A was cisplatin 30 mg/m2, irinotecan 60 mg/m2, capecitabine 1000 mg/d and MTD-B was cisplatin 20 mg/m2, irinotecan 90 mg/m2, capecitabine 1000 mg/d. An MTD was not formally established for part C. DLTs consisted of infection with neutropenia (1), diarrhea and fatigue (1), hypokalemia (1), diarrhea and febrile neutropenia (1) and C2 delay of ≥2 weeks or 25{\%} dose reduction in C1 due to neutropenia or thrombocytopenia (6). Seven patients had a partial response to treatment (four colorectal, one SCLC, one NSCLC, one unknown primary), twenty seven SD (53{\%}), twelve PD (24{\%}) and five NE (10{\%}). Conclusion: CIC was associated with moderate toxicity and only modest antitumor activity. We conclude that this regimen has insufficient activity to justify further study in the phase II setting.",
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A novel combination of cisplatin, irinotecan, and capecitabine in patients with advanced cancer. / Jefford, Michael; Michael, Michael; Rosenthal, Mark A.; Davis, Ian D.; Green, Michael; McClure, Bev; Smith, Jennifer; Waite, Brigid; Zalcberg, John.

In: Investigational New Drugs, Vol. 22, No. 2, 01.04.2004, p. 185-192.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - A novel combination of cisplatin, irinotecan, and capecitabine in patients with advanced cancer

AU - Jefford, Michael

AU - Michael, Michael

AU - Rosenthal, Mark A.

AU - Davis, Ian D.

AU - Green, Michael

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AU - Smith, Jennifer

AU - Waite, Brigid

AU - Zalcberg, John

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N2 - Background: We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen. Patients and methods: Intravenous cisplatin and irinotecan were to be administered on days 1 and 8, and oral capecitabine on days 1-14 of a 3-week cycle. The study was conducted in three parts. Part A: escalating doses of irinotecan (40 → 80 mg/m2) and capecitabine (1000 → 3300 mg/d) combined with a fixed dose of cisplatin (30 mg/m2). Part B: escalating doses of irinotecan (MTD-A → MTD-A + 40 mg/m2) with fixed doses of cisplatin (20 mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300 mg/d → 2600 mg/d) with fixed doses of cisplatin (20 mg/m2) and irinotecan (60 mg/m 2). Results: Of 51 eligible patients 27 (53%) were male, median age was 58 years and 88% had PS 0-1. Major primary disease sites were colorectal (24%), unknown (14%), stomach (14%), and pancreas (12%). MTD-A was cisplatin 30 mg/m2, irinotecan 60 mg/m2, capecitabine 1000 mg/d and MTD-B was cisplatin 20 mg/m2, irinotecan 90 mg/m2, capecitabine 1000 mg/d. An MTD was not formally established for part C. DLTs consisted of infection with neutropenia (1), diarrhea and fatigue (1), hypokalemia (1), diarrhea and febrile neutropenia (1) and C2 delay of ≥2 weeks or 25% dose reduction in C1 due to neutropenia or thrombocytopenia (6). Seven patients had a partial response to treatment (four colorectal, one SCLC, one NSCLC, one unknown primary), twenty seven SD (53%), twelve PD (24%) and five NE (10%). Conclusion: CIC was associated with moderate toxicity and only modest antitumor activity. We conclude that this regimen has insufficient activity to justify further study in the phase II setting.

AB - Background: We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen. Patients and methods: Intravenous cisplatin and irinotecan were to be administered on days 1 and 8, and oral capecitabine on days 1-14 of a 3-week cycle. The study was conducted in three parts. Part A: escalating doses of irinotecan (40 → 80 mg/m2) and capecitabine (1000 → 3300 mg/d) combined with a fixed dose of cisplatin (30 mg/m2). Part B: escalating doses of irinotecan (MTD-A → MTD-A + 40 mg/m2) with fixed doses of cisplatin (20 mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300 mg/d → 2600 mg/d) with fixed doses of cisplatin (20 mg/m2) and irinotecan (60 mg/m 2). Results: Of 51 eligible patients 27 (53%) were male, median age was 58 years and 88% had PS 0-1. Major primary disease sites were colorectal (24%), unknown (14%), stomach (14%), and pancreas (12%). MTD-A was cisplatin 30 mg/m2, irinotecan 60 mg/m2, capecitabine 1000 mg/d and MTD-B was cisplatin 20 mg/m2, irinotecan 90 mg/m2, capecitabine 1000 mg/d. An MTD was not formally established for part C. DLTs consisted of infection with neutropenia (1), diarrhea and fatigue (1), hypokalemia (1), diarrhea and febrile neutropenia (1) and C2 delay of ≥2 weeks or 25% dose reduction in C1 due to neutropenia or thrombocytopenia (6). Seven patients had a partial response to treatment (four colorectal, one SCLC, one NSCLC, one unknown primary), twenty seven SD (53%), twelve PD (24%) and five NE (10%). Conclusion: CIC was associated with moderate toxicity and only modest antitumor activity. We conclude that this regimen has insufficient activity to justify further study in the phase II setting.

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KW - Cisplatin

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