Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer

JCOG 9910-DI

Katsuhiko Naoki, Hiroshi Kunikane, Tomoki Fujii, Shuko Tsujimura, Naoya Hida, Hiroaki Okamoto, Koshiro Watanabe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: Combined paclitaxel and carboplatin is a standard regimen for inoperable non-small cell lung cancer (NSCLC). Although an every-3-week schedule is common, weekly paclitaxel is clinically effective for various cancers. A Phase I clinical trial was conducted to determine maximum-tolerated doses (MTDs) for weekly combined paclitaxel and carboplatin, and to evaluate anti-tumor response, toxicity and pharmacokinetics of paclitaxel in patients with inoperable NSCLC. Methods: Twenty patients with inoperable NSCLC received weekly carboplatin at area under the curve (AUC) = 2 mg/ml min and paclitaxel. Paclitaxel was escalated if MTD was not reached. Three patients each were entered at levels 1 and 2 (level 1, paclitaxel 50 mg/m2 and carboplatin AUC = 2 mg/ml min; level 2, 60/2), six at level 3 (70/ 2), five at level 4 (80/2) and three at level 5 (90/2). Results: One patient had grade 4 (G4) neutropenia at level 2, one had G3 hepatic toxicity at level 3 and one had G3 cardiac toxicity at level 4. MTD was not reached for all dose levels. Response rate (RR) was 35% (7/ 20) and median survival was 11.1 months. Severe neutropenia (G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (Cmax) and the duration of plasma concentration >50 ng/ml of paclitaxel. Conclusions: Weekly combined paclitaxel (up to 90 mg/m2) and carboplatin (AUC = 2 mg/ml min) was well tolerated. A higher dose intensity of paclitaxel can be given, and RR and survival are not less than the every-3-week protocol. The weekly regimen is an alternative for untreated inoperable NSCLC patients.

Original languageEnglish
Pages (from-to)569-575
Number of pages7
JournalJapanese Journal of Clinical Oncology
Volume39
Issue number9
DOIs
Publication statusPublished - 2009

Fingerprint

Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Pharmacokinetics
Area Under Curve
Maximum Tolerated Dose
Neutropenia
Clinical Trials, Phase I
Neoplasms
Appointments and Schedules
Survival Rate
Survival
Liver

Keywords

  • Carboplatin
  • Non-small cell lung cancer
  • Paclitaxel
  • Phase I
  • Weekly chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Radiology Nuclear Medicine and imaging

Cite this

Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer : JCOG 9910-DI. / Naoki, Katsuhiko; Kunikane, Hiroshi; Fujii, Tomoki; Tsujimura, Shuko; Hida, Naoya; Okamoto, Hiroaki; Watanabe, Koshiro.

In: Japanese Journal of Clinical Oncology, Vol. 39, No. 9, 2009, p. 569-575.

Research output: Contribution to journalArticle

Naoki, Katsuhiko ; Kunikane, Hiroshi ; Fujii, Tomoki ; Tsujimura, Shuko ; Hida, Naoya ; Okamoto, Hiroaki ; Watanabe, Koshiro. / Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer : JCOG 9910-DI. In: Japanese Journal of Clinical Oncology. 2009 ; Vol. 39, No. 9. pp. 569-575.
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abstract = "Objective: Combined paclitaxel and carboplatin is a standard regimen for inoperable non-small cell lung cancer (NSCLC). Although an every-3-week schedule is common, weekly paclitaxel is clinically effective for various cancers. A Phase I clinical trial was conducted to determine maximum-tolerated doses (MTDs) for weekly combined paclitaxel and carboplatin, and to evaluate anti-tumor response, toxicity and pharmacokinetics of paclitaxel in patients with inoperable NSCLC. Methods: Twenty patients with inoperable NSCLC received weekly carboplatin at area under the curve (AUC) = 2 mg/ml min and paclitaxel. Paclitaxel was escalated if MTD was not reached. Three patients each were entered at levels 1 and 2 (level 1, paclitaxel 50 mg/m2 and carboplatin AUC = 2 mg/ml min; level 2, 60/2), six at level 3 (70/ 2), five at level 4 (80/2) and three at level 5 (90/2). Results: One patient had grade 4 (G4) neutropenia at level 2, one had G3 hepatic toxicity at level 3 and one had G3 cardiac toxicity at level 4. MTD was not reached for all dose levels. Response rate (RR) was 35{\%} (7/ 20) and median survival was 11.1 months. Severe neutropenia (G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (Cmax) and the duration of plasma concentration >50 ng/ml of paclitaxel. Conclusions: Weekly combined paclitaxel (up to 90 mg/m2) and carboplatin (AUC = 2 mg/ml min) was well tolerated. A higher dose intensity of paclitaxel can be given, and RR and survival are not less than the every-3-week protocol. The weekly regimen is an alternative for untreated inoperable NSCLC patients.",
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T1 - Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer

T2 - JCOG 9910-DI

AU - Naoki, Katsuhiko

AU - Kunikane, Hiroshi

AU - Fujii, Tomoki

AU - Tsujimura, Shuko

AU - Hida, Naoya

AU - Okamoto, Hiroaki

AU - Watanabe, Koshiro

PY - 2009

Y1 - 2009

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AB - Objective: Combined paclitaxel and carboplatin is a standard regimen for inoperable non-small cell lung cancer (NSCLC). Although an every-3-week schedule is common, weekly paclitaxel is clinically effective for various cancers. A Phase I clinical trial was conducted to determine maximum-tolerated doses (MTDs) for weekly combined paclitaxel and carboplatin, and to evaluate anti-tumor response, toxicity and pharmacokinetics of paclitaxel in patients with inoperable NSCLC. Methods: Twenty patients with inoperable NSCLC received weekly carboplatin at area under the curve (AUC) = 2 mg/ml min and paclitaxel. Paclitaxel was escalated if MTD was not reached. Three patients each were entered at levels 1 and 2 (level 1, paclitaxel 50 mg/m2 and carboplatin AUC = 2 mg/ml min; level 2, 60/2), six at level 3 (70/ 2), five at level 4 (80/2) and three at level 5 (90/2). Results: One patient had grade 4 (G4) neutropenia at level 2, one had G3 hepatic toxicity at level 3 and one had G3 cardiac toxicity at level 4. MTD was not reached for all dose levels. Response rate (RR) was 35% (7/ 20) and median survival was 11.1 months. Severe neutropenia (G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (Cmax) and the duration of plasma concentration >50 ng/ml of paclitaxel. Conclusions: Weekly combined paclitaxel (up to 90 mg/m2) and carboplatin (AUC = 2 mg/ml min) was well tolerated. A higher dose intensity of paclitaxel can be given, and RR and survival are not less than the every-3-week protocol. The weekly regimen is an alternative for untreated inoperable NSCLC patients.

KW - Carboplatin

KW - Non-small cell lung cancer

KW - Paclitaxel

KW - Phase I

KW - Weekly chemotherapy

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