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Cancer Chemotherapy and Pharmacology

, Volume 60, Issue 5, pp 759–766 | Cite as

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane®) on three treatment schedules in patients with solid tumors

  • Thomas E. Stinchcombe
  • Mark A. Socinski
  • Christine M. Walko
  • Bert H. O’Neil
  • Frances A. Collichio
  • Anastasia Ivanova
  • Hua Mu
  • Michael J. Hawkins
  • Richard M. Goldberg
  • Celeste Lindley
  • E. Claire Dees
Original Article

Abstract

Purpose

Albumin-bound paclitaxel, ABI-007 (Abraxane®), has a different toxicity profile than solvent-based paclitaxel, including a lower rate of severe neutropenia. The combination of ABI-007 and carboplatin may have significant activity in a variety of tumor types including non-small and small cell lung cancer, ovarian cancer, and breast cancer. The purpose of this study was to determine the maximum tolerated dose (MTD) of ABI-007, on three different schedules in combination with carboplatin.

Methods

Forty-one patients with solid tumors were enrolled, and received ABI-007 in combination with carboplatin AUC of 6 on day 1. Group A received ABI-007 at doses ranging from 220 to 340 mg/m2 on day 1 every 21 days; group B received ABI-007 at 100 or 125 mg/m2 on days 1, 8, and 15 every 28 days; and group C received ABI-007 125 or 150 mg/m2 on days 1 and 8 every 21 days. Dose-limiting toxicities were assessed after the first cycle. Doses were escalated in cohorts of three to six patients. Fifteen patients participated in a pharmacokinetic study investigating the effects of the sequence of infusion. ABI-007 was infused first followed by carboplatin in cycle 1, and vice versa in cycle 2.

Results

The MTD of ABI-007 in combination with carboplatin was 300, 100, and 125 mg/m2 in groups A, B, and C, respectively. Myelosuppression was the primary dose limiting toxicity. No unexpected or new toxicities were reported. Sequence of infusion did not affect either the pharmacokinetics of ABI-007 or the degree of neutropenia. Responses were seen in melanoma, lung, bladder, esophageal, pancreatic, breast cancer, and cancer of unknown primary.

Conclusions

The recommended dose for phase II studies of ABI-007 in combination with carboplatin (AUC of 6) is 300, 100, 125 mg/m2 for the schedules A, B, and C, respectively. The combination of ABI-007 and carboplatin is well tolerated and active in this heavily pretreated patient population.

Keywords

Dose-limiting toxicity Maximum tolerated dose Melanoma Non-small-cell lung cancer Small-cell lung cancer Clinical trial 

Notes

Acknowledgments

The authors thank Paul E Jones, Tammy Allred, Susan Natoli and Henry Bell for their help with the study, and the patients whose participation made this trial possible. Financially supported by the Grant for General Clinical Research Center (Grant # RR00046) and Abraxis Bioscience.

References

  1. 1.
    Socinski MA (1999) Single-agent paclitaxel in the treatment of advanced non-small cell lung cancer. Oncologist 4(5):408–416PubMedGoogle Scholar
  2. 2.
    Crown J, O’Leary M (2000) The taxanes: an update. Lancet 355(9210):1176–1178PubMedCrossRefGoogle Scholar
  3. 3.
    Gelderblom H, Verweij J, Nooter K, Sparreboom A (2001) Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 37(13):1590–1598PubMedCrossRefGoogle Scholar
  4. 4.
    Authier N, Gillet JP, Fialip J, Eschalier A, Coudore F (2001) Assessment of neurotoxicity following repeated cremophor/ethanol injections in rats. Neurotox Res 3(3):301–306PubMedCrossRefGoogle Scholar
  5. 5.
    Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P et al (2005) Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 23(31):7794–7803PubMedCrossRefGoogle Scholar
  6. 6.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346(2):92–98PubMedCrossRefGoogle Scholar
  7. 7.
    Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA et al (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 21(17):3194–3200PubMedCrossRefGoogle Scholar
  8. 8.
    Burris H 3rd, Yardley D, Jones S, Houston G, Broome C, Thompson D et al (2004) Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment for patients with metastatic breast cancer. J Clin Oncol 22(9):1621–1629PubMedCrossRefGoogle Scholar
  9. 9.
    Rowinsky EK, Gilbert MR, McGuire WP, Noe DA, Grochow LB, Forastiere AA et al (1991) Sequences of taxol and cisplatin: a phase I and pharmacologic study. J Clin Oncol 9(9):1692–1703PubMedGoogle Scholar
  10. 10.
    Huizing MT, Giaccone G, van Warmerdam LJ, Rosing H, Bakker PJ, Vermorken JB et al (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(1):317–329PubMedGoogle Scholar
  11. 11.
    Markman M, Elson P, Kulp B, Peterson G, Zanotti K, Webster K et al (2003) Carboplatin plus paclitaxel combination chemotherapy: impact of sequence of drug administration on treatment-induced neutropenia. Gynecol Oncol 91(1):118–122PubMedCrossRefGoogle Scholar
  12. 12.
    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, National cancer institute of the United States, National cancer institute of Canada. J Natl Cancer Inst 92(3):205–216PubMedCrossRefGoogle Scholar
  13. 13.
    Calvert AH, Newell DR, Gumbrell LA, O’Reilly S, Burnell M, Boxall FE et al (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7(11):1748–1756PubMedGoogle Scholar
  14. 14.
    Ibrahim NK, Samuels B, Page R, Doval D, Patel KM, Rao SC et al (2005) Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J Clin Oncol 23(25):6019–6026PubMedCrossRefGoogle Scholar
  15. 15.
    Ibrahim NK, Desai N, Legha S, Soon-Shiong P, Theriault RL, Rivera E et al (2002) Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res 8(5):1038–1044PubMedGoogle Scholar
  16. 16.
    Kosmidis P, Mylonakis N, Skarlos D, Samantas E, Dimopoulos M, Papadimitriou C et al (2000) Paclitaxel (175 mg/m2) plus carboplatin (6 AUC) versus paclitaxel (225 mg/m2) plus carboplatin (6 AUC) in advanced non-small-cell lung cancer (NSCLC): a multicenter randomized trial. Hellenic cooperative oncology group (HeCOG). Ann Oncol 11(7):799–805PubMedCrossRefGoogle Scholar
  17. 17.
    Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550PubMedCrossRefGoogle Scholar
  18. 18.
    Nyman DW, Campbell KJ, Hersh E, Long K, Richardson K, Trieu V et al (2005) Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. J Clin Oncol 23(31):7785–7793PubMedCrossRefGoogle Scholar
  19. 19.
    Allerton JP, Hagenstad CT, Webb RT, Smith GB, Birch R, Goggins TF et al (2006) A phase II evaluation of the combination of paclitaxel protein-bound and carboplatin in the first line treatment of advanced non-small cell lung cancer (NSCLC). J Clin Oncol (ASCO Annual Meetings Proceedings) 24(18S):7127 (abstract)Google Scholar
  20. 20.
    Hawkins MJ, Georgy M, Makhson A, Cheporov S, Sergey O, Yablonsky P et al (2006) Dose escalation study of nab-paclitaxel followed by carboplatin a first line therapy in advanced non-small cell lung cancer (NSCLC). J Clin Oncol (ASCO Annual Meetings Proceedings) 24(18S):7132 (abstract)Google Scholar
  21. 21.
    Socinski MA, Schell MJ, Peterman A, Bakri K, Yates S, Gitten R et al (2002) Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J Clin Oncol 20(5):1335–1343PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Thomas E. Stinchcombe
    • 1
    • 5
  • Mark A. Socinski
    • 1
  • Christine M. Walko
    • 2
  • Bert H. O’Neil
    • 1
  • Frances A. Collichio
    • 1
  • Anastasia Ivanova
    • 3
  • Hua Mu
    • 4
  • Michael J. Hawkins
    • 4
  • Richard M. Goldberg
    • 1
  • Celeste Lindley
    • 2
  • E. Claire Dees
    • 1
  1. 1.Department of Hematology/Oncology, Developmental Therapeutics Group Lineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel HillUSA
  2. 2.School of PharmacyUniversity of North CarolinaChapel HillUSA
  3. 3.Department of BiostaticsLineberger Comprehensive Cancer CenterChapel HillUSA
  4. 4.Abraxis BioScienceLos AngelesUSA
  5. 5.Chapel HillUSA

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