Abstract
The continuous infusion of fluorouracil presents a superior pharmacological profile than its bolus administration, while vinorelbine is a new drug associated with good clinical activity in pretreated metastatic breast cancer. We investigated the combination of this two antitumor drugs with the aim to determine a tolerant and active second-line therapy in metastatic pretreated patients.
Patients and methods.Fifty six patients pretreated with chemotherapy received a median of six cycles [2–11] of fluorouracil, 700 mg/m2 for 5 day-continuous i.v. infusion and vinorelbine, 20 mg/m2 on days 1 and 6, every three weeks. The inclusion and evaluation criteria required measurable disease by conventional clinical and/or instrumental means.
Findings.Iatrogenic toxicity in 340 administered cycles was mild: stomatitis ==11% (Grade 3 ==5%), constipation and abdominal pain ==12, G2 neutropenia ==4, G1 thrombocytopenia ==0.5. In nine cases moderate infections occurred and six women experienced catheter related complications. Complete and partial remissions were observed in 12% and 36% of evaluable patients, respectively. In particular major tumor regression was documented in 28% of anthracyclines or taxol unresponsive cases.
Conclusions.This drug combination is active in metastatic pretreated breast cancer patients and devoid of serious iatrogenic toxicity. Although it deserves future optimization, for instance with the inclusion of oral fluoropirimidines, it represents a good choice for second-line or non cross-resistant regimens.
Similar content being viewed by others
References
Huan S, Pazdur R, Singhakowinta A, Samal B, Vaitkevicius V: Low dose continous infusion 5-fluorouracil. Cancer 63: 419–422, 1989
Jabboury K, Holmes F, Hortobagyi G: 5-fluorouracil rechallenge by pretreated infusion in metastatic breast cancer. Cancer 64: 793–797, 1989
Lokich J: Optimal schedule for 5-fluorouracil chemotherapy: intermittent bolus or continuous infusion. Am J Clin Oncol 8: 445–448, 1985
Fumuleau P, Delgado FM, Delazier T, et al.: Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 11: 1245–1212, 1993
Terenziani M, Demicheli R, Brambilla C, et al.: Vinorelbine: an active non cross-resistant drug in advanced breast cancer. Results from a phase II study. Breast Cancer Res Treat 39: 285–291, 1996
Gasparini G, Caffo O, Barni S, et al.: Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients. J Clin Oncol 12: 2094–2101, 1994
Dieras U, Extra JM, Bellissant E, et al.: Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer. Results of a phase II study using a sequential group method. J Clin Oncol 12: 3097–3104, 1996
Dogliotti L, Berruti A, Sperone P, et al.: Vinorelbine and protracted infusional 5-fluorouracil is a very active and manageable schema for heavily pretreated advanced breast cancer patients. Am Soc Clin Oncol 432: 114, 1999
Nolè F, De Braud F, Aapro M, et al.: Phase I-II study of vinorelbine in combination with 5-fluorouracil and folinic acid as first-line chemotherapy in metastatic breast cancer: a regimen with a low subjective toxic burden. Ann Oncol 8: 865–870, 1997
Budman DR, et al.: Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine. J Clin Oncol 16: 1795–1802, 1998
Blum JL, et al.: A multicentric phase II trial of Xeloda (capecitabine) in paclitaxel refractory breast cancer. Proc Am Soc Clin Oncol 17: 47, 1998
Schilsky RL, Hohneker J, Ratain NJ, et al.: Phase I clinical and pharmacological study of eniluracil plus fluorouracil in patients with advanced cancer. J Clin Oncol 16: 1450–1457, 1998
Baker SP, Khor SP, Adjei AA, et al.: Pharmacokinetic, oral bioavability and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase. J Clin Oncol 14: 3085–3096, 1996
Rights and permissions
About this article
Cite this article
Zambetti, M., Mariani, G., Demicheli, R. et al. Five-day infusion fluorouracil plus vinorelbine in women with breast cancer previously treated with anthracyclines and paclitaxel. Breast Cancer Res Treat 62, 135–139 (2000). https://doi.org/10.1023/A:1006445713773
Issue Date:
DOI: https://doi.org/10.1023/A:1006445713773