A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer

Katsuyuki Hotta, Hiroshi Ueoka, Katsuyuki Kiura, Masahiro Tabata, Shoichi Kuyama, Ken Satoh, Toshiyuki Kozuki, Akiko Hisamoto, Shinobu Hosokawa, Keiichi Fujiwara, Mitsune Tanimoto

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine the maximum-tolerated dose (MTD) of irinotecan and paclitaxel in this two-drug combination, and to investigate a sequence-dependent effect in the pharmacokinetics of these drugs, we conducted a phase I study in chemo-naïve patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with stage IIIB/IV NSCLC were enrolled in this study. Both irinotecan and paclitaxel were administered on days 1 and 8, and repeated every 3 weeks. The starting dose of both drugs was 40 mg/m2 which was then alternately increased by 10 mg/m2 increments. In the first cycle, irinotecan was initially administered and followed by paclitaxel infusion, while the sequence of drug administration was reversed in the second cycle. Blood samples for pharmacokinetic analysis were obtained on day 1 of the first and second cycles. Results: Nine patients received a total of 12 cycles, which were evaluated for toxicity and efficacy. The main hematological toxicity was neutropenia. Grades 3 or more neutropenia was observed in 67% of cycles at dose level 2. The main non-hematological toxicities were grade 3 febrile neutropenia, supraventricular arrhythmia, and grade 2 hepatic dysfunction. The MTD of irinotecan and paclitaxel were 40 and 50 mg/m2, respectively. In the pharmacokinetic analysis, the maximum concentration of paclitaxel was elevated in a dose-dependent manner. There was a trend toward elevation of the area under the plasma concentration-time curve (AUC) of irinotecan and a decline of the AUC of paclitaxel in cycle 1 (irinotecan followed by paclitaxel), compared with those in cycle 2 (paclitaxel followed by irinotecan). Hepatic toxicity was strongly associated with the AUC of irinotecan (r=0.894,P

Original languageEnglish
Pages (from-to)77-84
Number of pages8
JournalLung Cancer
Volume45
Issue number1
DOIs
Publication statusPublished - Jul 2004

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irinotecan
Paclitaxel
Non-Small Cell Lung Carcinoma
Pharmacokinetics
Area Under Curve
Maximum Tolerated Dose
Neutropenia
Pharmaceutical Preparations
Febrile Neutropenia
Liver
Drug Combinations

Keywords

  • Irinotecan
  • Non-platinum regimen
  • Non-small cell lung cancer
  • Paclitaxel
  • Pharmacokinetics
  • Phase I study

ASJC Scopus subject areas

  • Oncology

Cite this

A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer. / Hotta, Katsuyuki; Ueoka, Hiroshi; Kiura, Katsuyuki; Tabata, Masahiro; Kuyama, Shoichi; Satoh, Ken; Kozuki, Toshiyuki; Hisamoto, Akiko; Hosokawa, Shinobu; Fujiwara, Keiichi; Tanimoto, Mitsune.

In: Lung Cancer, Vol. 45, No. 1, 07.2004, p. 77-84.

Research output: Contribution to journalArticle

Hotta, Katsuyuki ; Ueoka, Hiroshi ; Kiura, Katsuyuki ; Tabata, Masahiro ; Kuyama, Shoichi ; Satoh, Ken ; Kozuki, Toshiyuki ; Hisamoto, Akiko ; Hosokawa, Shinobu ; Fujiwara, Keiichi ; Tanimoto, Mitsune. / A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer. In: Lung Cancer. 2004 ; Vol. 45, No. 1. pp. 77-84.
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abstract = "Purpose: To determine the maximum-tolerated dose (MTD) of irinotecan and paclitaxel in this two-drug combination, and to investigate a sequence-dependent effect in the pharmacokinetics of these drugs, we conducted a phase I study in chemo-na{\"i}ve patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with stage IIIB/IV NSCLC were enrolled in this study. Both irinotecan and paclitaxel were administered on days 1 and 8, and repeated every 3 weeks. The starting dose of both drugs was 40 mg/m2 which was then alternately increased by 10 mg/m2 increments. In the first cycle, irinotecan was initially administered and followed by paclitaxel infusion, while the sequence of drug administration was reversed in the second cycle. Blood samples for pharmacokinetic analysis were obtained on day 1 of the first and second cycles. Results: Nine patients received a total of 12 cycles, which were evaluated for toxicity and efficacy. The main hematological toxicity was neutropenia. Grades 3 or more neutropenia was observed in 67{\%} of cycles at dose level 2. The main non-hematological toxicities were grade 3 febrile neutropenia, supraventricular arrhythmia, and grade 2 hepatic dysfunction. The MTD of irinotecan and paclitaxel were 40 and 50 mg/m2, respectively. In the pharmacokinetic analysis, the maximum concentration of paclitaxel was elevated in a dose-dependent manner. There was a trend toward elevation of the area under the plasma concentration-time curve (AUC) of irinotecan and a decline of the AUC of paclitaxel in cycle 1 (irinotecan followed by paclitaxel), compared with those in cycle 2 (paclitaxel followed by irinotecan). Hepatic toxicity was strongly associated with the AUC of irinotecan (r=0.894,P",
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T1 - A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer

AU - Hotta, Katsuyuki

AU - Ueoka, Hiroshi

AU - Kiura, Katsuyuki

AU - Tabata, Masahiro

AU - Kuyama, Shoichi

AU - Satoh, Ken

AU - Kozuki, Toshiyuki

AU - Hisamoto, Akiko

AU - Hosokawa, Shinobu

AU - Fujiwara, Keiichi

AU - Tanimoto, Mitsune

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AB - Purpose: To determine the maximum-tolerated dose (MTD) of irinotecan and paclitaxel in this two-drug combination, and to investigate a sequence-dependent effect in the pharmacokinetics of these drugs, we conducted a phase I study in chemo-naïve patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with stage IIIB/IV NSCLC were enrolled in this study. Both irinotecan and paclitaxel were administered on days 1 and 8, and repeated every 3 weeks. The starting dose of both drugs was 40 mg/m2 which was then alternately increased by 10 mg/m2 increments. In the first cycle, irinotecan was initially administered and followed by paclitaxel infusion, while the sequence of drug administration was reversed in the second cycle. Blood samples for pharmacokinetic analysis were obtained on day 1 of the first and second cycles. Results: Nine patients received a total of 12 cycles, which were evaluated for toxicity and efficacy. The main hematological toxicity was neutropenia. Grades 3 or more neutropenia was observed in 67% of cycles at dose level 2. The main non-hematological toxicities were grade 3 febrile neutropenia, supraventricular arrhythmia, and grade 2 hepatic dysfunction. The MTD of irinotecan and paclitaxel were 40 and 50 mg/m2, respectively. In the pharmacokinetic analysis, the maximum concentration of paclitaxel was elevated in a dose-dependent manner. There was a trend toward elevation of the area under the plasma concentration-time curve (AUC) of irinotecan and a decline of the AUC of paclitaxel in cycle 1 (irinotecan followed by paclitaxel), compared with those in cycle 2 (paclitaxel followed by irinotecan). Hepatic toxicity was strongly associated with the AUC of irinotecan (r=0.894,P

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