Cancer Chemotherapy and Pharmacology

, Volume 55, Issue 6, pp 552–558

Sequence effect of docetaxel and carboplatin on toxicity, tumor response and pharmacokinetics in non-small-cell lung cancer patients: a phase I study of two sequences

  • Maki Ando
  • Hideo Saka
  • Yuichi Ando
  • Hironobu Minami
  • Takafumi Kuzuya
  • Masashi Yamamoto
  • Atsushi Watanabe
  • Shuzo Sakai
  • Kaoru Shimokata
  • Yoshinori Hasegawa
Original Article



To investigate sequence effects on toxicity, tumor response and pharmacokinetics of docetaxel and carboplatin, together with a determination of the maximum-tolerated dose (MTD) and recommended dose for each schedule.

Patients and methods

A total of 46 chemotherapy-naive patients with advanced non-small-cell lung cancer were randomized to receive docetaxel before (schedule A) or after (schedule B) carboplatin. The dose levels studied were [docetaxel (mg/m2)/carboplatin (mg×min/ml)] 50/5, 60/5, 60/6, 60/7, and 70/6. Treatment cycles were repeated every 3 or 4 weeks unless disease progression or undue toxicity occurred.


Of the 46 patients, 44 were assessable for toxicity and received a total of 84 cycles. The major dose-limiting toxicity was neutropenia. When the docetaxel dose was 60 mg/m2, the carboplatin MTD was deemed to be AUC 7 in both schedules. When the docetaxel dose was escalated to 70 mg/m2, the carboplatin MTD was reached in schedule A, and the dose-limiting toxicity was not observed in schedule B. Tumor response was observed in 4 of 22 patients (18%) with schedule A and 8 of 19 (42%) with schedule B. Clearances of both drugs were not affected by sequence: 111.2±26.8 ml/min and 107.8±29.0 ml/min for carboplatin (P=0.69), and 26.7±8.3 l/h and 22.8±7.0 l/h for docetaxel (P=0.19) in schedules A and B, respectively.


Carboplatin AUC 6 followed by docetaxel 70 mg/m2 was a favorable regimen for phase II study because of likely lower toxicity and a potentially higher response rate than the reverse sequence schedule. The mechanism of the sequence effects on toxicity and tumor response could not be explained by the pharmacokinetic interactions.


Maximum-tolerated dose Recommended dose Dose-limiting toxicity Chemotherapy 


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Maki Ando
    • 1
  • Hideo Saka
    • 2
  • Yuichi Ando
    • 3
  • Hironobu Minami
    • 4
  • Takafumi Kuzuya
    • 5
  • Masashi Yamamoto
    • 6
  • Atsushi Watanabe
    • 7
  • Shuzo Sakai
    • 8
  • Kaoru Shimokata
    • 1
  • Yoshinori Hasegawa
    • 1
  1. 1.Department of Medicine, Division of Respiratory DiseasesNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of Internal Medicine, Division of Respiratory DiseasesNational Nagoya HospitalNagoyaJapan
  3. 3.Department of Clinical OncologySaitama Medical SchoolSaitamaJapan
  4. 4.National Cancer Center Hospital EastKashiwaJapan
  5. 5.Department of Hospital PharmacyNagoya University Graduate School of MedicineNagoyaJapan
  6. 6.Nagoya Ekisaikai HospitalNagoyaJapan
  7. 7.Aichi-ken Koseiren Kosei HospitalAichiJapan
  8. 8.Japanese Red Cross Nagoya First HospitalNagoyaJapan

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