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

Abstract

This effective combination chemotherapy of vinorelbine, 5-fluorouracil and folinic acid is comparable to other first-line regimens in terms of efficacy, and is subjectively well tolerated, thus deserving a test in randomized trials in the advanced and adjuvant settings.

Phase II study of weekly vinorelbine and 24-h infusion of high-dose 5-fluorouracil plus leucovorin as first-line treatment of advanced breast cancer

“…Although survival is not a major end point for evaluation of efficacy in phase II trials, the median overall survival of 25 months in this study was favourably within the range of other previously reported major protocols of anthracycline-based regimens (Ross et al, 1985;Clavel and Catimel, 1993;Jassem et al, 2001;Biganzoli et al, 2002;Sledge et al, 2003), taxane-based regimens (Jassem et al, 2001;Biganzoli et al, 2002;Sledge et al, 2003), and vinorelbinebased regimens (Dieras et al, 1996a;Nole et al, 1997;Norris et al, 2000).…”

“…The overall response rate of 70.0% (95% confidence interval: 54 -84%) was within the range (40 -70%) of previously reported major protocols of anthracycline-based regimens (Ross et al, 1985;Clavel and Catimel, 1993;Jassem et al, 2001;Biganzoli et al, 2002;Sledge et al, 2003), taxane-based regimens (Jassem et al, 2001;Biganzoli et al, 2002;Sledge et al, 2003), and anthracyclineand-taxane-based regimens (Razis and Fountzilas, 2001;Sledge et al, 2003). Previously, studies from other series using vinorelbine and different administration schedules of 5-FU and LV have also demonstrated a good efficacy in breast cancer (Dieras et al, 1996a;Nole et al, 1997). However, the 5-day loading schedule of 5-FU created significant treatment-related toxicity, which may limit its clinical use (Dieras et al, 1996a).…”

“…The median response duration and overall survival were 12.3 and 23 months, respectively. Nole et al (1997) confirmed similar data in combination with vinorelbine, 5-FU, and LV with a response rate of 62%. However, the 5-day loading schedule of 5-FU (50 mg m À2 per day for 5 consecutive days as a continuous infusion) had significant treatment-related toxicity (such as 90% grade 3/4 neutropenia and 37% grade 3/4 mucositis, respectively), which may limit its clinical use (Dieras et al, 1996a).…”

“…In contrast, the paclitaxelrelated neuropathy was found to be one of the dose-limiting toxicities in paclitaxel-containing regimens for breast cancer (Postma et al, 1995;Forsyth et al, 1997;Gelmon et al, 1999). Other major toxicities, including diarrohea and stomatitis, were of lesser severity than for other major regimens using vinorelbine and a 5-day schedule of 5-FU and LV (Dieras et al, 1996a;Nole et al, 1997). Neutropenia and leucopenia were not less severe than other reported regimens using vinorelbine and 5-FU; however, the doses, schedules, and G-CSF support of these regimens were essentially different from the current regimen (Kornek et al, 1998;Lombardi et al, 2000).…”

Efectividad de 5-fluoruracilo y vinorelbina en pacientes multitratadas por cáncer de mama metastásico

“…La asociación de 5FU/vinorelbina tiene ventajas teóri-cas que son: mecanismos diferentes de citotoxicidad, resistencia y una baja sobreposición de sus efectos tó-xicos 17,18 . En seis estudios fase II se ha reportado la efectividad y toxicidad de esta combinación, todos ellos con dosis diferentes de fluoruracilo y vinorelbina [23][24][25][26] . En nuestro estudio, con el fin de minimizar los efectos tóxicos pero sin restar efectividad, redujimos la frecuencia de vinorelbina a cada 21 días y se compensó con 5FU en infusión continua.…”