Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 4/2009

01.09.2009 | Original Article

Phase II study of an all-oral combination of vinorelbine with capecitabine in patients with metastatic breast cancer

verfasst von: Franco Nolè, D. Crivellari, R. Mattioli, G. Pinotti, P. Foa, E. Verri, R. Fougeray, M. Brandely, A. Goldhirsch

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2009

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Combination of intravenous (i.v.) vinorelbine and capecitabine was shown to be feasible and effective in metastatic breast cancer (MBC). In an effort to improve patient convenience and to prolong infusion-free survival, we investigated in first-line treatment a regimen combining oral vinorelbine and capecitabine in a phase II study.

Patients and methods

Fifty-two patients (median age, 60 years) with MBC received the combination consisting of oral vinorelbine 60 mg/m2 on days 1, 8 and 15 plus capecitabine 1,000 mg/m2 bid given from day 1 to day 14 in an open-label, multicentre phase II study [the recommended doses were established in a phase I study (Nolé et al. in Ann Oncol 17:332–339, 2006)]. Cycles were repeated every 3 weeks.

Results

Seventy-nine percent of the patients had received prior adjuvant chemotherapy and 81% presented with visceral involvement. The median number of administered cycles per patient was 7 (range 1–18). Twenty-three responses were documented and validated by an independent panel review, yielding response rates of 44.2% (95% CI, 30.5–58.7) in the 52 enrolled patients and 54.8% (95% CI, 38.7–70.2) in the 42 evaluable patients. Median progression-free survival and median overall survival were 8.4 and 25.8 months, respectively. Neutropenia was the main dose-limiting toxicity but complications were uncommon, only one patient having experienced febrile neutropenia. Other frequently reported adverse events included, fatigue, nausea, vomiting, diarrhoea and constipation, stomatitis and hand-foot syndrome, which were rarely severe.

Conclusions

This regimen combining oral vinorelbine with capecitabine is effective and manageable in the first-line treatment of MBC. Oral vinorelbine on days 1, 8 and 15 with capecitabine from days 1 to 14 every 3 weeks represents a convenient option which offers an all-oral treatment to the patients and prolongs their infusion-free survival.
Literatur
1.
Zurück zum Zitat Nolé F, Catania G, Sanna G et al (2006) Dose finding and pharmacokinetic study of an all-oral combination of oral vinorelbine and capecitabine for patients with metastatic breast cancer. Ann Oncol 17:332–339 Nolé F, Catania G, Sanna G et al (2006) Dose finding and pharmacokinetic study of an all-oral combination of oral vinorelbine and capecitabine for patients with metastatic breast cancer. Ann Oncol 17:332–339
2.
Zurück zum Zitat Binet S, Fellous A, Lataste H, Krikorian A, Couzinier JP, Meininger V (1989) In situ analysis of the action of navelbine on various types of microtubules using immunofluorescence. Semin Oncol 16:5–8PubMed Binet S, Fellous A, Lataste H, Krikorian A, Couzinier JP, Meininger V (1989) In situ analysis of the action of navelbine on various types of microtubules using immunofluorescence. Semin Oncol 16:5–8PubMed
3.
Zurück zum Zitat Saif MW, Katirzoglou NA, Syrigos KN (2008) Capecitabine: an overview of the side effects and their management. Anticancer Drugs 19:447–464PubMed Saif MW, Katirzoglou NA, Syrigos KN (2008) Capecitabine: an overview of the side effects and their management. Anticancer Drugs 19:447–464PubMed
4.
Zurück zum Zitat Fumoleau P, Delgado FM, Delozier T et al (1993) Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 11:1245–1252PubMed Fumoleau P, Delgado FM, Delozier T et al (1993) Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 11:1245–1252PubMed
5.
Zurück zum Zitat Garcia-Conde J, Lluch A, Martin M et al (1994) Phase II trial of weekly i.v. vinorelbine in first-line advanced breast cancer chemotherapy. Ann Oncol 5:854–857PubMed Garcia-Conde J, Lluch A, Martin M et al (1994) Phase II trial of weekly i.v. vinorelbine in first-line advanced breast cancer chemotherapy. Ann Oncol 5:854–857PubMed
6.
Zurück zum Zitat Romero A, Rabinovich MG, Vallejo CT et al (1994) Vinorelbine as first-line chemotherapy for metastatic breast carcinoma. J Clin Oncol 12:336–341PubMed Romero A, Rabinovich MG, Vallejo CT et al (1994) Vinorelbine as first-line chemotherapy for metastatic breast carcinoma. J Clin Oncol 12:336–341PubMed
7.
Zurück zum Zitat Weber BL, Vogel C, Jones S et al (1995) Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer. J Clin Oncol 13:2722–2730PubMed Weber BL, Vogel C, Jones S et al (1995) Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer. J Clin Oncol 13:2722–2730PubMed
8.
Zurück zum Zitat Bruno S, Puerto VL, Mickiewicz E et al (1995) Phase II trial of weekly i.v. vinorelbine as single agent in first-line advanced breast cancer chemotherapy. The Latin-American experience. Am J Clin Oncol 18:392–396PubMedCrossRef Bruno S, Puerto VL, Mickiewicz E et al (1995) Phase II trial of weekly i.v. vinorelbine as single agent in first-line advanced breast cancer chemotherapy. The Latin-American experience. Am J Clin Oncol 18:392–396PubMedCrossRef
9.
Zurück zum Zitat Twelves CJ, Dobbs NA, Curnow A et al (1994) A phase II, multicentre, UK study of vinorelbine in advanced breast cancer. Br J Cancer 70:990–993PubMed Twelves CJ, Dobbs NA, Curnow A et al (1994) A phase II, multicentre, UK study of vinorelbine in advanced breast cancer. Br J Cancer 70:990–993PubMed
10.
Zurück zum Zitat Terenziani M, Demicheli R, Brambilla C et al (1996) Vinorelbine: an active, non-cross-resistant drug in advanced breast cancer: results from a phase II study. Breast Cancer Res Treat 39:285–291PubMedCrossRef Terenziani M, Demicheli R, Brambilla C et al (1996) Vinorelbine: an active, non-cross-resistant drug in advanced breast cancer: results from a phase II study. Breast Cancer Res Treat 39:285–291PubMedCrossRef
11.
Zurück zum Zitat Trillet-Lenoir V, Sommer H, Delozier T et al. (2004) Oral vinorelbine in metastatic breast cancer: long-term results of 2 phase II studies. Eur J Cancer 2(3): abst 279 Trillet-Lenoir V, Sommer H, Delozier T et al. (2004) Oral vinorelbine in metastatic breast cancer: long-term results of 2 phase II studies. Eur J Cancer 2(3): abst 279
12.
Zurück zum Zitat Freyer G, Delozier T, Lichinister M et al (2003) Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 21:35–40PubMed Freyer G, Delozier T, Lichinister M et al (2003) Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 21:35–40PubMed
13.
Zurück zum Zitat Gridelli C, Parlier Y, Brandely M et al (2003) Oral chemotherapy and upper gastro-intestinal tolerance improvement of nausea and vomiting in non-small cell lung cancer patients treated with oral navelbine and standard antiemetic prophylaxis. Eur J Cancer 1:5 abst 801 Gridelli C, Parlier Y, Brandely M et al (2003) Oral chemotherapy and upper gastro-intestinal tolerance improvement of nausea and vomiting in non-small cell lung cancer patients treated with oral navelbine and standard antiemetic prophylaxis. Eur J Cancer 1:5 abst 801
14.
Zurück zum Zitat Liu G, Franssen E, Fitch MI et al (1997) Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 15:110–115PubMed Liu G, Franssen E, Fitch MI et al (1997) Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 15:110–115PubMed
15.
Zurück zum Zitat Marty M, Fumoleau P, Adenis A et al (2001) Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol 12:1643–1649PubMedCrossRef Marty M, Fumoleau P, Adenis A et al (2001) Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol 12:1643–1649PubMedCrossRef
16.
Zurück zum Zitat Blum JL, Jones SE, Budzar AV et al (1999) Multicenter phase II study of capecitabine in paclitaxel-refractory mestastatic breast cancer. J Clin Oncol 17:485–493PubMed Blum JL, Jones SE, Budzar AV et al (1999) Multicenter phase II study of capecitabine in paclitaxel-refractory mestastatic breast cancer. J Clin Oncol 17:485–493PubMed
17.
Zurück zum Zitat Fumoleau P, Largillier R, Clippe C et al (2004) Multicenter phase II study evaluating capecitabine monotherapy in patients with anthracyclines and taxane pretreated metastatic breast cancer. Eur J Cancer 40:536–542PubMedCrossRef Fumoleau P, Largillier R, Clippe C et al (2004) Multicenter phase II study evaluating capecitabine monotherapy in patients with anthracyclines and taxane pretreated metastatic breast cancer. Eur J Cancer 40:536–542PubMedCrossRef
18.
Zurück zum Zitat Sawada N, Fujimoto-Ouchi F, Ishikawa T et al (2002) Antitumor activity of combination therapy with capecitabine plus vinorelbine, and capecitabine plus gemcitabine in human tumor xenograft models. Proc Am Assoc Cancer Res 43:1088a abstract 5388 Sawada N, Fujimoto-Ouchi F, Ishikawa T et al (2002) Antitumor activity of combination therapy with capecitabine plus vinorelbine, and capecitabine plus gemcitabine in human tumor xenograft models. Proc Am Assoc Cancer Res 43:1088a abstract 5388
19.
Zurück zum Zitat Lorusso V, Spada M, Giampaglia M et al (2006) Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (MBC). A phase II study of the GOIM (Gruppo Oncologico d’ell’Italia Meridionale). Ann Oncol 17(Suppl 7):15–17 Lorusso V, Spada M, Giampaglia M et al (2006) Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (MBC). A phase II study of the GOIM (Gruppo Oncologico d’ell’Italia Meridionale). Ann Oncol 17(Suppl 7):15–17
20.
Zurück zum Zitat Ahn JH, Kim SB, Kim TW, Ahn SH et al (2004) Capecitabine and vinorelbine in patients with metastatic breast cancer previously treated with anthracyclines and taxane. J Korean Med Sci 19:547–553PubMedCrossRef Ahn JH, Kim SB, Kim TW, Ahn SH et al (2004) Capecitabine and vinorelbine in patients with metastatic breast cancer previously treated with anthracyclines and taxane. J Korean Med Sci 19:547–553PubMedCrossRef
21.
Zurück zum Zitat Davis AJ, Brew S, Gebski VJ et al (2007) Multicenter phase II study of combination chemotherapy with capecitabine and intravenous vinorelbine in patients with pretreated metastatic breast cancer. Asia Pac J Clin Oncol 3:1–7CrossRef Davis AJ, Brew S, Gebski VJ et al (2007) Multicenter phase II study of combination chemotherapy with capecitabine and intravenous vinorelbine in patients with pretreated metastatic breast cancer. Asia Pac J Clin Oncol 3:1–7CrossRef
22.
Zurück zum Zitat Welt A, Von Minckwitz G, Oberhoff C et al (2005) Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer. Ann Oncol 16:64–69PubMedCrossRef Welt A, Von Minckwitz G, Oberhoff C et al (2005) Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer. Ann Oncol 16:64–69PubMedCrossRef
23.
Zurück zum Zitat Hess D, Thurlimann B, Pagani O et al (2004) Capecitabine and vinorelbine in elderly patients (≥65 years) with metastatic breast cancer: a phase I trial (SAKK 25/99). Ann Oncol 15:1760–1765PubMedCrossRef Hess D, Thurlimann B, Pagani O et al (2004) Capecitabine and vinorelbine in elderly patients (≥65 years) with metastatic breast cancer: a phase I trial (SAKK 25/99). Ann Oncol 15:1760–1765PubMedCrossRef
24.
Zurück zum Zitat Stuart N, Bishop L, Johnson SRD et al (2003) Vinorelbine and capecitabine for advanced breast cancer. A phase II study showing good activity and potential for further development. Proc Am Soc Clin Oncol (Abstr 183) Stuart N, Bishop L, Johnson SRD et al (2003) Vinorelbine and capecitabine for advanced breast cancer. A phase II study showing good activity and potential for further development. Proc Am Soc Clin Oncol (Abstr 183)
25.
Zurück zum Zitat Ghosn M, Kattan J, Farhat F et al (2006) Phase II trial of capecitabine and vinorelbine as first-line chemotherapy for metastatic breast cancer patients. Anticancer Res 26:2451–2456PubMed Ghosn M, Kattan J, Farhat F et al (2006) Phase II trial of capecitabine and vinorelbine as first-line chemotherapy for metastatic breast cancer patients. Anticancer Res 26:2451–2456PubMed
26.
Zurück zum Zitat Pizzo PA 1993 Management of fever in patients with cancer and treatment-induced neutropenia. New Eng J Med 32:8 1323–32 Pizzo PA 1993 Management of fever in patients with cancer and treatment-induced neutropenia. New Eng J Med 32:8 1323–32
27.
Zurück zum Zitat O’Shaughnessy J, Blum J, Moiseyenko V et al (2001) Randomised open-label, phase II trial of oral capecitabine (xeloda) versus a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 12:1247–1254CrossRef O’Shaughnessy J, Blum J, Moiseyenko V et al (2001) Randomised open-label, phase II trial of oral capecitabine (xeloda) versus a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 12:1247–1254CrossRef
Metadaten
Titel
Phase II study of an all-oral combination of vinorelbine with capecitabine in patients with metastatic breast cancer
verfasst von
Franco Nolè
D. Crivellari
R. Mattioli
G. Pinotti
P. Foa
E. Verri
R. Fougeray
M. Brandely
A. Goldhirsch
Publikationsdatum
01.09.2009
Verlag
Springer-Verlag
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 4/2009
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-008-0915-3

Weitere Artikel der Ausgabe 4/2009

Cancer Chemotherapy and Pharmacology 4/2009 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.