Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer

Eric Bleickardt, Athanassios Argiris, Randy Rich, Kathi Blum, Anne McKeon, Harold Tara, Daniel Zelterman, Barbara Burtness, Marianne J. Davies, John R. Murren

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background. Docetaxel and irinotecan have additive or synergistic activity in vitro and in vivo as well as differing toxicities and unique mechanisms of action. We conducted a phase I trial to determine the maximum-tolerated dose of docetaxel and irinotecan given on a weekly schedule. Methods. Eligible patients had advanced, incurable, solid tumors. Docetaxel was administered as a 1-hour infusion and escalated over four dose levels (25, 30, 35, and 40 mg/m 2) followed by irinotecan administered over 30 minutes at a fixed dose of 50 mg/m2. Treatment was administered weekly for four weeks followed by two weeks of rest. To improve tolerability, the schedule was modified to weekly administration for two weeks with one week of rest, and irinotecan was escalated over 3 dose levels (55, 60, and 65 mg/m2) with docetaxel fixed at 35 mg/m2. Results. Forty-four patients were treated and the most common dose-limiting toxicity was diarrhea observed in 11% of patients. Severe neutropenia was rare (grade 4: 2%, grade 3: 23%). Other nonhematologic toxicities included nausea/vomiting, dehydration and fatigue. Partial responses occurred in two patients with pancreatic cancer, and one patient each with non-small cell lung and esophageal cancer. Conclusions. Weekly docetaxel and irinotecan is a promising non-cisplatin doublet with preliminary evidence of activity in advanced solid tumors. Diarrhea is the predominant dose-limiting toxicity but unlike the every 3 weeks schedule myelosuppression is modest. The recommended phase II doses are docetaxel 35 mg/m2 and irinotecan 60 mg/m2 on days 1 and 8 of a 21-day schedule. Phase II trials of this regimen are ongoing or planned in lung, head and neck, stomach, esophageal, and pancreatic cancers.

Original languageEnglish (US)
Pages (from-to)646-650
Number of pages5
JournalCancer Biology and Therapy
Volume1
Issue number6
StatePublished - Nov 2002
Externally publishedYes

Fingerprint

irinotecan
docetaxel
Appointments and Schedules
Neoplasms
Esophageal Neoplasms
Pancreatic Neoplasms
Diarrhea
Maximum Tolerated Dose
Head and Neck Neoplasms
Neutropenia
Dehydration
Non-Small Cell Lung Carcinoma
Nausea
Stomach Neoplasms
Vomiting
Fatigue

Keywords

  • CPT-11
  • Docetaxel
  • Irinotecan
  • Lung cancer
  • Pancreatic cancer
  • Phase I

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Bleickardt, E., Argiris, A., Rich, R., Blum, K., McKeon, A., Tara, H., ... Murren, J. R. (2002). Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer. Cancer Biology and Therapy, 1(6), 646-650.

Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer. / Bleickardt, Eric; Argiris, Athanassios; Rich, Randy; Blum, Kathi; McKeon, Anne; Tara, Harold; Zelterman, Daniel; Burtness, Barbara; Davies, Marianne J.; Murren, John R.

In: Cancer Biology and Therapy, Vol. 1, No. 6, 11.2002, p. 646-650.

Research output: Contribution to journalArticle

Bleickardt, E, Argiris, A, Rich, R, Blum, K, McKeon, A, Tara, H, Zelterman, D, Burtness, B, Davies, MJ & Murren, JR 2002, 'Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer', Cancer Biology and Therapy, vol. 1, no. 6, pp. 646-650.
Bleickardt E, Argiris A, Rich R, Blum K, McKeon A, Tara H et al. Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer. Cancer Biology and Therapy. 2002 Nov;1(6):646-650.
Bleickardt, Eric ; Argiris, Athanassios ; Rich, Randy ; Blum, Kathi ; McKeon, Anne ; Tara, Harold ; Zelterman, Daniel ; Burtness, Barbara ; Davies, Marianne J. ; Murren, John R. / Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer. In: Cancer Biology and Therapy. 2002 ; Vol. 1, No. 6. pp. 646-650.
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abstract = "Background. Docetaxel and irinotecan have additive or synergistic activity in vitro and in vivo as well as differing toxicities and unique mechanisms of action. We conducted a phase I trial to determine the maximum-tolerated dose of docetaxel and irinotecan given on a weekly schedule. Methods. Eligible patients had advanced, incurable, solid tumors. Docetaxel was administered as a 1-hour infusion and escalated over four dose levels (25, 30, 35, and 40 mg/m 2) followed by irinotecan administered over 30 minutes at a fixed dose of 50 mg/m2. Treatment was administered weekly for four weeks followed by two weeks of rest. To improve tolerability, the schedule was modified to weekly administration for two weeks with one week of rest, and irinotecan was escalated over 3 dose levels (55, 60, and 65 mg/m2) with docetaxel fixed at 35 mg/m2. Results. Forty-four patients were treated and the most common dose-limiting toxicity was diarrhea observed in 11{\%} of patients. Severe neutropenia was rare (grade 4: 2{\%}, grade 3: 23{\%}). Other nonhematologic toxicities included nausea/vomiting, dehydration and fatigue. Partial responses occurred in two patients with pancreatic cancer, and one patient each with non-small cell lung and esophageal cancer. Conclusions. Weekly docetaxel and irinotecan is a promising non-cisplatin doublet with preliminary evidence of activity in advanced solid tumors. Diarrhea is the predominant dose-limiting toxicity but unlike the every 3 weeks schedule myelosuppression is modest. The recommended phase II doses are docetaxel 35 mg/m2 and irinotecan 60 mg/m2 on days 1 and 8 of a 21-day schedule. Phase II trials of this regimen are ongoing or planned in lung, head and neck, stomach, esophageal, and pancreatic cancers.",
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AU - Argiris, Athanassios

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AU - McKeon, Anne

AU - Tara, Harold

AU - Zelterman, Daniel

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AB - Background. Docetaxel and irinotecan have additive or synergistic activity in vitro and in vivo as well as differing toxicities and unique mechanisms of action. We conducted a phase I trial to determine the maximum-tolerated dose of docetaxel and irinotecan given on a weekly schedule. Methods. Eligible patients had advanced, incurable, solid tumors. Docetaxel was administered as a 1-hour infusion and escalated over four dose levels (25, 30, 35, and 40 mg/m 2) followed by irinotecan administered over 30 minutes at a fixed dose of 50 mg/m2. Treatment was administered weekly for four weeks followed by two weeks of rest. To improve tolerability, the schedule was modified to weekly administration for two weeks with one week of rest, and irinotecan was escalated over 3 dose levels (55, 60, and 65 mg/m2) with docetaxel fixed at 35 mg/m2. Results. Forty-four patients were treated and the most common dose-limiting toxicity was diarrhea observed in 11% of patients. Severe neutropenia was rare (grade 4: 2%, grade 3: 23%). Other nonhematologic toxicities included nausea/vomiting, dehydration and fatigue. Partial responses occurred in two patients with pancreatic cancer, and one patient each with non-small cell lung and esophageal cancer. Conclusions. Weekly docetaxel and irinotecan is a promising non-cisplatin doublet with preliminary evidence of activity in advanced solid tumors. Diarrhea is the predominant dose-limiting toxicity but unlike the every 3 weeks schedule myelosuppression is modest. The recommended phase II doses are docetaxel 35 mg/m2 and irinotecan 60 mg/m2 on days 1 and 8 of a 21-day schedule. Phase II trials of this regimen are ongoing or planned in lung, head and neck, stomach, esophageal, and pancreatic cancers.

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