Phase I trial of weekly paclitaxel in advanced lung cancer

Wallace Akerley, Michael Glantz, Hak Choy, Vishram Rege, Sundaresan Sambandam, Plakyil Joseph, Loren Yee, Brigid Rodrigues, Patti Wingate, Louis Leone

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Abstract

Purpose: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum- tolerated dose (MTD) of paclitaxel using an extended weekly schedule. Patients and Methods: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/μL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. Results: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle I. Neutropenia was dose-limiting. Four-teen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% ± 10%) patients demonstrated an objective response. Conclusion: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

Original languageEnglish (US)
Pages (from-to)153-158
Number of pages6
JournalJournal of Clinical Oncology
Volume16
Issue number1
DOIs
StatePublished - Jan 1 1998

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Paclitaxel
Lung Neoplasms
Appointments and Schedules
Maximum Tolerated Dose
Neutropenia
Non-Small Cell Lung Carcinoma
Granulocytes
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Akerley, W., Glantz, M., Choy, H., Rege, V., Sambandam, S., Joseph, P., ... Leone, L. (1998). Phase I trial of weekly paclitaxel in advanced lung cancer. Journal of Clinical Oncology, 16(1), 153-158. https://doi.org/10.1200/JCO.1998.16.1.153
Akerley, Wallace ; Glantz, Michael ; Choy, Hak ; Rege, Vishram ; Sambandam, Sundaresan ; Joseph, Plakyil ; Yee, Loren ; Rodrigues, Brigid ; Wingate, Patti ; Leone, Louis. / Phase I trial of weekly paclitaxel in advanced lung cancer. In: Journal of Clinical Oncology. 1998 ; Vol. 16, No. 1. pp. 153-158.
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abstract = "Purpose: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum- tolerated dose (MTD) of paclitaxel using an extended weekly schedule. Patients and Methods: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/μL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50{\%} of patients developed unacceptable toxicity and received more than 80{\%} of the intended first-cycle dose. Results: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle I. Neutropenia was dose-limiting. Four-teen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35{\%} ± 10{\%}) patients demonstrated an objective response. Conclusion: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.",
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Akerley, W, Glantz, M, Choy, H, Rege, V, Sambandam, S, Joseph, P, Yee, L, Rodrigues, B, Wingate, P & Leone, L 1998, 'Phase I trial of weekly paclitaxel in advanced lung cancer', Journal of Clinical Oncology, vol. 16, no. 1, pp. 153-158. https://doi.org/10.1200/JCO.1998.16.1.153

Phase I trial of weekly paclitaxel in advanced lung cancer. / Akerley, Wallace; Glantz, Michael; Choy, Hak; Rege, Vishram; Sambandam, Sundaresan; Joseph, Plakyil; Yee, Loren; Rodrigues, Brigid; Wingate, Patti; Leone, Louis.

In: Journal of Clinical Oncology, Vol. 16, No. 1, 01.01.1998, p. 153-158.

Research output: Contribution to journalArticle

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T1 - Phase I trial of weekly paclitaxel in advanced lung cancer

AU - Akerley, Wallace

AU - Glantz, Michael

AU - Choy, Hak

AU - Rege, Vishram

AU - Sambandam, Sundaresan

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AU - Yee, Loren

AU - Rodrigues, Brigid

AU - Wingate, Patti

AU - Leone, Louis

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N2 - Purpose: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum- tolerated dose (MTD) of paclitaxel using an extended weekly schedule. Patients and Methods: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/μL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. Results: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle I. Neutropenia was dose-limiting. Four-teen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% ± 10%) patients demonstrated an objective response. Conclusion: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

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