Oncology

Clinical Study

Efficacy and Tolerability of Capecitabine with Weekly Paclitaxel for Patients with Metastatic Breast Cancer: A Phase II Report of the SAKK

Gick U.a · Rochlitz C.c · Mingrone W.d · Pestalozzi B.e · Rauch D.f · Ballabeni P.b · Lanz D.b · Hess V.a · Aebi S.a

Author affiliations

aDepartment of Medical Oncology, University Hospital Inselspital, and bSwiss Group for Clinical Cancer Research, Coordinating Center, Bern, cDepartment of Medical Oncology, University Hospital, Basel, dDepartment of Medical Oncology, Cantonal Hospital, Aarau, eDepartment of Medical Oncology, University Hospital, Zurich, and fDepartment of Medical Oncology, Regional Hospital, Thun, Switzerland

Keywords: Metastatic breast cancerCapecitabinePaclitaxelPhase II trial

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Oncology 2006;71:54–60
https://doi.org/10.1159/000100449

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Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: July 07, 2006
Accepted: November 18, 2006
Published online: April 13, 2007
Issue release date: April 2007

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 3

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

Abstract

Background: Paclitaxel and capecitabine have proven activity in the treatment of metastatic breast cancer (MBC). Paclitaxel increases the expression of thymidine phosphorylase, the enzyme that activates capecitabine. The purpose of this study was to evaluate the efficacy and tolerability of capecitabine in combination with weekly paclitaxel largely as first-line therapy in patients with MBC. Patients and Methods: From April 2002 to September 2004, 19 patients with MBC received oral capecitabine (1,000 mg/m2 twice daily on days 1–14) plus i.v. paclitaxel (80 mg/m2 on days 1, 8 and 15) in a 21-day cycle for a maximum of 6 cycles. Results: After a median follow-up of 19.3 months the overall response rate was 63% with 1 complete response (5%) and 11 partial responses (58%). Disease was stabilized in 1 patient (5%) and 3 patients had progressive disease (16%). Three patients were unable to be assessed for response to treatment. Median time to progression was 3.3 months, median time to treatment failure 3.0 months and median overall survival 13.8 months. A substantial number of patients experienced major side effects. The most common treatment-related adverse events were hand-foot syndrome (53%; grade 3: 37%), alopecia (42%; grade 3: 26%), diarrhea (32%; grade 3: 11%) and neurotoxicity (32%; grade 3: 16%). Hematologic toxicities were uncommon. Conclusion: The combination of capecitabine and paclitaxel appears to be active in MBC but the safety profile with the dosages used in this trial was unacceptably high and led to a short time to treatment failure. However, based on the efficacy data alternative schedules deserve further evaluation.

© 2006 S. Karger AG, Basel



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References

  1. Nabholtz JM: Treatment of metastatic breast cancer; in Harris J, Lippman ME, Morrow M, Osborne CK (eds): Diseases of the Breast. Philadelphia, Lippincott Williams & Wilkins, 2004, p 1089.
  2. Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998;34:1274–1281.
    External Resources
  3. Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs 2000;18:343–354.
    External Resources
  4. Blum JL, Jones SE, Buzdar AU, Lo Russo PM, Kuter I, Vogel C, Osterwalder B, Burger HU, Brown CS, Griffin T: Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1999;17:485–493.
    External Resources
  5. Blum JL, Dieras V, Lo Russo PM, Horton J, Rutman O, Buzdar A, Osterwalder B: Multicenter, phase II study of capecitabine in taxane-pretreated metastatic breast carcinoma patients. Cancer 2001;92:1759–1768.
    External Resources
  6. Talbot DC, Moiseyenko V, Van Belle S, O’Reilly SM, Alba Conejo E, Ackland S, Eisenberg P, Melnychuk D, Pienkowski T, Burger HU, Laws S, Osterwalder B: Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines. Br J Cancer 2002;86:1367–1372.
    External Resources
  7. Reichardt P, Von Minckwitz G, Thuss-Patience PC, Jonat W, Kolbl H, Janicke F, Kieback DG, Kuhn W, Schindler AE, Mohrmann S, Kaufmann M, Luck HJ: Multicenter phase II study of oral capecitabine (Xeloda®) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapy. Ann Oncol 2003;14:1227–1233.
    External Resources
  8. O’Shaughnessy J: The evolving role of capecitabine in breast cancer. Clin Breast Cancer 2003:S20–S25.
    External Resources
  9. Perez EA: Paclitaxel in breast cancer. Oncologist 1998;3:373–389.
    External Resources
  10. Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R: Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol 2001;19:4216–4223.
    External Resources
  11. Seidman AD, Berry D, Cirrincione C, et al: Phase III study of weekly paclitaxel via 1-hour infusion vs. standard 3-hour infusion every third week in the treatment of metastatic breast cancer, with trastuzumab for HER2+ metastatic breast cancer (MBC), and randomized for trastuzumab for HER2 normal MBC. Proc Am Soc Clin Oncol 2004;22:512.
  12. Villalona-Calero MA, Blum JL, Jones SE, Diab S, Elledge R, Khoury P, Von Hoff D, Kraynak M, Moczygemba J, Kromelis P, Griffin T, Rowinsky EK: A phase I and pharmacologic study of capecitabine and paclitaxel in breast cancer patients. Ann Oncol 2001;12:605–614.
    External Resources
  13. O’Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R: Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 2002;20:2812–2823.
    External Resources
  14. Uhlmann C, Ballabeni P, Rijken N, Brauchli P, Mingrone W, Rauch D, Pestalozzi BC, Rochlitz C, Aebi S: Capecitabine with weekly paclitaxel for advanced breast cancer: a phase I dose-finding trial. Oncology 2004;67:117–122.
    External Resources
  15. Perez-Manga G, Batista N, Constenla M, Guillem V, Carabantes F, Ahlgren J, Castellanos J, Gonzalez-Baron M, Villman K, Söderberg K, Casinello J, Murias A, Regueiro P: Efficacy and safety profile of capecitabine (Xeloda) in combination with paclitaxel (P) in patients with locally advanced or metastastic breast cancer: preliminary results of a phase II study. Breast Cancer Res Treat 2000;64:124.
  16. Gradishar WJ, Meza LA, Amin B, Samid D, Hill T, Chen YM, Lower EE, Marcom PK: Capecitabine plus paclitaxel as front-line combination therapy for metastatic breast cancer: a multicenter phase II study. J Clin Oncol 2004;22:2321–2327.
    External Resources
  17. Simon R: Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1–10.
    External Resources
  18. Kaplan E, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–481.
    External Resources
  19. Bari M, M.R. DA, Sartori D, Pappagallo GL, Azzarello G, Rosetti F, Silvestri B, Gaion F, Iop A, Vinante O: Capecitabin (C) plus weekly paclitaxel (wP) in metastatic breast cancer (M-BC): a phase II study. Proc Am Soc Clin Oncol 2003;22:66.
  20. Batista N, Perez-Manga G, Constenla M, Ruiz A, Carabantes F, Castellanos J, Gonzalez Baron M, Villman K, Soderberg M, Ahlgren J, Casinello J, Regueiro P, Murias A: Phase II study of capecitabine in combination with paclitaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Br J Cancer 2004;90:1740–1746.
    External Resources
  21. Blum JL, Dees C, Negron A, McMahon R, Boehm KA, Asmar L, O’Shaughnessy J: A phase II trial of combination therapy with capecitabine and weekly paclitaxel for metastatic breast cancer (MBC): preliminary results in taxane-naïve patients. Breast Cancer Res Treat 2004;88(Suppl 1):S202.
  22. Blum JL, Dees EC, Asmar L, Vukelja S, McMahon R, Amare M, Gill D, Llegbodu D, Boehm KA, O’Shaughnessy J: Results of a phase II trial of combination therapy with oral capecitabine and weekly paclitaxel for metastatic breast cancer: preliminary results in taxane pretreated women. Breast Cancer Res Treat 2005;94(Suppl 1):S280.
  23. Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H: Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 1998;4:1013–1019.
    External Resources
  24. Susnjar S, Bosnjak S, Radulovic S, Stevanovic J, Gajic-Dobrosavlc M, Kreacic M: Weekly paclitaxel (Tax) and capecitabine (Cap) for metastatic breast cancer (MBC) patients (pts) previously treated with anthracycline-containing therapy: a phase I dose-finding study. Proc Am Soc Clin Oncol 2005;23:90s.
  25. Mackey JR, Tonkin K, Scarfe AG, Koski S, Smylie M, Au J, Bodnar D, Smith SW, Soulieres D: Final results of a phase II clinical trial of weekly docetaxel (T) in combination with capecitabine (X) in anthracycline pre-treated metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2003;22:42.
  26. Di Costanzo F, Gasperoni S, Papaldo P, Bilancia D, Manzione L, Landucci E, Mazzoni F, Cognetti F: Weekly paclitaxel plus capecitabine in advanced breast cancer patients: dose-finding trial of GOIRC and GOL. Ann Oncol 2005;17:79–84.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: July 07, 2006
Accepted: November 18, 2006
Published online: April 13, 2007
Issue release date: April 2007

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 3

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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2006, Vol.71, No. 1-2

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