Safety and pharmacokinetic study of nab-paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer

Isamu Okamoto, Nobuyuki Yamamoto, Kaoru Kubota, Yuichiro Ohe, Naoyuki Nogami, Haruyasu Murakami, Hidetoshi Yamaya, Katsuhiro Ono, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a Cremophor EL-free formulation of paclitaxel newly designed to avoid solvent-related toxicities. We have evaluated the safety, tolerability, pharmacokinetics, and tumor response profile of weekly nab-paclitaxel (100 mg/m2) infusion together with administration of carboplatin at an area under the curve (AUC) of 6 every 3 weeks in Japanese patients with advanced non-small cell lung cancer (NSCLC). Methods Nab-paclitaxel (100 mg/m2) was administered without steroid or antihistamine premedication as a 30-min intravenous infusion once a week in combination with carboplatin at an AUC of 6 on day 1 of repeated 21-day cycles. The pharmacokinetics of both drugs were analyzed, and both adverse events and treatment response were monitored. Results Eighteen patients were enrolled in the study. The most frequent treatment-related toxicities of grade 3 or 4 were neutropenia (67%), leukopenia (50%), and anemia (22%). No severe hypersensitivity reactions were observed despite the lack of premedication, and no unexpected or new toxicities were detected. Pharmacokinetics analysis did not reveal any substantial drug-drug interactions. Seven partial responses were observed among the 18 evaluable patients, yielding a treatment response rate of 38.9%. Conclusions The combination of nab-paclitaxel (100 mg/m2) administered weekly and carboplatin at an AUC of 6 every 3 weeks was well tolerated in Japanese patients with advanced NSCLC. This combination therapy also showed promising antitumor activity and was not associated with relevant pharmacokinetic interactions.

Original languageEnglish
Pages (from-to)1132-1137
Number of pages6
JournalInvestigational New Drugs
Volume30
Issue number3
DOIs
Publication statusPublished - Jun 1 2012
Externally publishedYes

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Carboplatin
Non-Small Cell Lung Carcinoma
Nanoparticles
Pharmacokinetics
Area Under Curve
Safety
Drug Therapy
Premedication
Histamine Antagonists
Leukopenia
Therapeutics
Paclitaxel
Neutropenia
Drug Interactions
Intravenous Infusions
Pharmaceutical Preparations
Anemia
Hypersensitivity
Steroids
Albumin-Bound Paclitaxel

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

Safety and pharmacokinetic study of nab-paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer. / Okamoto, Isamu; Yamamoto, Nobuyuki; Kubota, Kaoru; Ohe, Yuichiro; Nogami, Naoyuki; Murakami, Haruyasu; Yamaya, Hidetoshi; Ono, Katsuhiro; Nakagawa, Kazuhiko.

In: Investigational New Drugs, Vol. 30, No. 3, 01.06.2012, p. 1132-1137.

Research output: Contribution to journalArticle

Okamoto, Isamu ; Yamamoto, Nobuyuki ; Kubota, Kaoru ; Ohe, Yuichiro ; Nogami, Naoyuki ; Murakami, Haruyasu ; Yamaya, Hidetoshi ; Ono, Katsuhiro ; Nakagawa, Kazuhiko. / Safety and pharmacokinetic study of nab-paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer. In: Investigational New Drugs. 2012 ; Vol. 30, No. 3. pp. 1132-1137.
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AU - Kubota, Kaoru

AU - Ohe, Yuichiro

AU - Nogami, Naoyuki

AU - Murakami, Haruyasu

AU - Yamaya, Hidetoshi

AU - Ono, Katsuhiro

AU - Nakagawa, Kazuhiko

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AB - Background Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a Cremophor EL-free formulation of paclitaxel newly designed to avoid solvent-related toxicities. We have evaluated the safety, tolerability, pharmacokinetics, and tumor response profile of weekly nab-paclitaxel (100 mg/m2) infusion together with administration of carboplatin at an area under the curve (AUC) of 6 every 3 weeks in Japanese patients with advanced non-small cell lung cancer (NSCLC). Methods Nab-paclitaxel (100 mg/m2) was administered without steroid or antihistamine premedication as a 30-min intravenous infusion once a week in combination with carboplatin at an AUC of 6 on day 1 of repeated 21-day cycles. The pharmacokinetics of both drugs were analyzed, and both adverse events and treatment response were monitored. Results Eighteen patients were enrolled in the study. The most frequent treatment-related toxicities of grade 3 or 4 were neutropenia (67%), leukopenia (50%), and anemia (22%). No severe hypersensitivity reactions were observed despite the lack of premedication, and no unexpected or new toxicities were detected. Pharmacokinetics analysis did not reveal any substantial drug-drug interactions. Seven partial responses were observed among the 18 evaluable patients, yielding a treatment response rate of 38.9%. Conclusions The combination of nab-paclitaxel (100 mg/m2) administered weekly and carboplatin at an AUC of 6 every 3 weeks was well tolerated in Japanese patients with advanced NSCLC. This combination therapy also showed promising antitumor activity and was not associated with relevant pharmacokinetic interactions.

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