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

Abstract

Purpose

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.

Results

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.

Conclusions

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.

Keywords

Maximum-tolerated dose Recommended dose Dose-limiting toxicity Chemotherapy 

References

  1. 1.
    Ando Y, Minami H, Saka H, Ando M, Sakai S, Shimokata K (1997) Adjustment of creatinine clearance improves accuracy of Calvert’s formula for carboplatin dosing. Br J Cancer 76:1067–1071Google Scholar
  2. 2.
    Belani CP, Hadeed V, Ramanathan R, Lembersky B, Agarwala S, Trump D, Jacobs S, Finley G, Hofacker J (1997) Docetaxel and carboplatin: a phase I and pharmacokinetic trial for advanced non-hematologic malignancies. Proc Am Soc Clin Oncol 220aGoogle Scholar
  3. 3.
    Bonomi PD, Finkelstein DM, Ruckdeschel JC, Blum RH, Green MD, Mason B, Hahn R, Tormey DC, Harris J, Comis R, Glick J (1989) Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol 7:1602–1613Google Scholar
  4. 4.
    Calvert AH, Harland SJ, Newell DR, Siddik ZH, Jones AC, McElwain TJ, Raju S, Wiltshaw E, Smith IE, Baker JM, Peckham MJ, Harrap KR (1982) Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II. Cancer Chemother Pharmacol 9:140–147Google Scholar
  5. 5.
    Catimel G, Verweij J, Mattijssen V, Hanauske A, Piccart M, Wanders J, Franklin H, Le Bail N, Clavel M, Kaye SB (1994) Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol 5:533–537Google Scholar
  6. 6.
    Cerny T, Kaplan S, Pavlidis N, Schoffski P, Epelbaum R, van Meerbeek J, Wanders J, Franklin HR, Kaye S (1994) Docetaxel (Taxotere) is active in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG). Br J Cancer 70:384–387PubMedGoogle Scholar
  7. 7.
    Extra JM, Rousseau F, Bruno R, Clavel M, Le Bail N, Marty M (1993) Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion. Cancer Res 53:1037–1042Google Scholar
  8. 8.
    Fossella FV, Lee JS, Murphy WK, Lippman SM, Calayag M, Pang A, Chasen M, Shin DM, Glisson B, Benner S, Huber M, Perez-Soler R, Hong WK, Raber M (1994) Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. J Clin Oncol 12:1238–1244PubMedGoogle Scholar
  9. 9.
    Fossella FV, Lee JS, Berille J, Hong WK (1995) Summary of phase II data of docetaxel (Taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer. Semin Oncol 22:22–29Google Scholar
  10. 10.
    Francis P, Schneider J, Hann L, Balmaceda C, Barakat R, Phillips M, Hakes T (1994) Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer. J Clin Oncol 12:2301–2308Google Scholar
  11. 11.
    Francis PA, Rigas JR, Kris MG, Pisters KM, Orazem JP, Woolley KJ, Heelan RT (1994) Phase II trial of docetaxel in patients with stage III and IV non-small-cell lung cancer. J Clin Oncol 12:1232–1237PubMedGoogle Scholar
  12. 12.
    Giannakakis T, Ziras N, Kakolyris S, Mavroudis D, Androulakis N, Agelaki S, Parashos M, Sarra E, Dimou T, Hatzidaki D, Vlachonikolis J, Georgoulias V (2000) Docetaxel in combination with carboplatin for the treatment of advanced non-small cell lung carcinoma: a multicentre phase I study. Eur J Cancer 36:742–747Google Scholar
  13. 13.
    Harland SJ, Newell DR, Siddik ZH, Chadwick R, Calvert AH, Harrap KR (1984) Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function. Cancer Res 44:1693–1697Google Scholar
  14. 14.
    Huizing MT, Giaccone G, van Warmerdam LJ, Rosing H, Bakker PJ, Vermorken JB, Postmus PE, van Zandwijk N, Koolen MG, ten Bokkel Huinink WW, van der Vijgh WJ, Bierhorst FJ, Lai A, Dalesio O, Pinedo HM, Veenhof CH, Beijnen JH (1997) Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre. J Clin Oncol 15:317–329Google Scholar
  15. 15.
    Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J, Cordier R, Finet C, Berchier MC, Sergysels R, Mommen P, Paesmans M (1990) A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. J Clin Oncol 8:1556–1562Google Scholar
  16. 16.
    Kunitoh H, Watanabe K, Onoshi T, Furuse K, Niitani H, Taguchi T (1996) Phase II trial of docetaxel in previously untreated advanced non-small-cell lung cancer: a Japanese cooperative study. J Clin Oncol 14:1649–1655Google Scholar
  17. 17.
    LeRoy AF, Wehling ML, Sponseller HL, Friauf WS, Solomon RE, Dedrick RL, Litterst CL, Gram TE, Guarino AM, Becker DA (1977) Analysis of platinum in biological materials by flameless atomic absorption spectrophotometry. Biochem Med 18:184–191CrossRefPubMedGoogle Scholar
  18. 18.
    McCollum AD, Catalano PJ, Haller DG, Mayer RJ, Macdonald JS, Benson AB III, Fuchs CS (2002) Outcomes and toxicity in African-American and Caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer. J Natl Cancer Inst 94:1160–1167Google Scholar
  19. 19.
    Millward MJ, Zalcberg J, Bishop JF, Webster LK, Zimet A, Rischin D, Toner GC, Laird J, Cosolo W, Urch M, Bruno R, Loret C, James R, Blanc C (1997) Phase I trial of docetaxel and cisplatin in previously untreated patients with advanced non-small-cell lung cancer. J Clin Oncol 15:750–758Google Scholar
  20. 20.
    National Cancer Institute: Common Toxicity Criteria (NCI-CTC). Revised 2nd edn. http://ctep.info.nih.gov
  21. 21.
    Oka M, Fukuda M, Nagashima S, Kinoshita A, Soda H, Doi S, Narasaki F, Suenaga M, Takatani H, Nakamura Y, Kawabata S, Tsurutani J, Kanda T, Kohno S (2001) Phase I study of second-line chemotherapy with docetaxel and carboplatin in advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 48:446–450Google Scholar
  22. 22.
    Pronk LC, Schellens JH, Planting AS, van den Bent MJ, Hilkens PH, van der Burg ME, de Boer-Dennert M, Ma J, Blanc C, Harteveld M, Bruno R, Stoter G, Verweij J (1997) Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors. J Clin Oncol 15:1071–1079Google Scholar
  23. 23.
    Rowinsky EK, Gilbert MR, McGuire WP, Noe DA, Grochow LB, Forastiere AA, Ettinger DS, Lubejko BG, Clark B, Sartorius SE, Cornblath DR, Hendricks CB, Donehower RC (1991) Sequences of taxol and cisplatin: a phase I and pharmacologic study. J Clin Oncol 9:1692–1703PubMedGoogle Scholar
  24. 24.
    Vici P, Belli F, Di Lauro L, Amodio A, Conti F, Foggi P, Gionfra T, Morelli MF, Botti C, Ferraironi A, Lopez M (2001) Docetaxel in patients with anthracycline-resistant advanced breast cancer. Oncology 60:60–65Google Scholar
  25. 25.
    WHO (1979) Handbook for reporting results of cancer treatment (publication 48). World Health Organization, GenevaGoogle Scholar

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

Personalised recommendations