A prospective, randomized phase III trial comparing combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil with vinorelbine plus doxorubicin in the treatment of advanced breast carcinoma

Abstract

BACKGROUND A prospective, multicenter, randomized, Phase III trial comparing the efficacy of combination chemotherapy with 5‐fluorouracil, doxorubicin, and cyclophosphamide (FAC) with a combination of vinorelbine and doxorubicin (NA) in the treatment of patients with advanced breast carcinoma was undertaken. METHODS One hundred and seventy‐seven patients who previously were untreated for recurrent or metastatic breast carcinoma were entered into the study; 7 patients could not be assessed. The final analysis relates to 85 patients who were treated with FAC and 85 patients who were treated with NA, of whom 21 (25%) and 44 (52%), respectively, had received prior adjuvant chemotherapy. RESULTS The overall response rates were similar for the two treatments and were unaffected by prior exposure to adjuvant therapy; overall response rate (ORR) for FAC was 74% (95% confidence interval [95% CI], 65–83%), and the ORR for NA was 75% (95% CI, 66–84%). The activity of NA in patients with liver involvement was greater than that of FAC in terms of survival. Overall survivals were similar, with a median of 17.3 months for patients receiving FAC and 17.8 months for patients receiving NA. Severe toxicity was uncommon with World Health Organization Grade 3–4 neutropenia affecting only 7% of patients in each arm of the study. NA was associated with a higher incidence of mild to moderate constipation, neurotoxicity, and phlebitis, whereas FAC produced a slight excess of mild cardiotoxicity. CONCLUSIONS The efficacy of these two regimens is very similar, although NA may be more active in a subset of patients with visceral metastatic disease, particularly liver involvement. It is clear that, in a direct comparison with an established three‐drug regimen, the newer two‐drug combination of NA demonstrated equivalent activity with no significant excess of Grade 3–4 toxicity. Cancer 1999;85:1091–7. © 1999 American Cancer Society.

Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial

“…It is worth stressing that the reported rates of haematological toxicity rely heavily on the frequency of blood count assessment. They could range from 7% to 84% for neutropaenia, 1% to 21% for anaemia or from 1% to 9% for thrombocytopaenia (Stewart et al, 1997;Blajman et al, 1999;FESG, 2000;Pacini et al, 2000;Bonneterre et al, 2004;Zielinski et al, 2005). A slightly lower toxicity of chemotherapy with respect to anaemia and thrombopaenia was even observed in the H-DHA group.…”

Activity and Safety of Vinorelbine Combined with Doxorubicin or Fluorouracil as First-Line Therapy in Advanced Breast Cancer: A Stratified Phase II Study

“…The risk of granulocytopenia associated with these combination regimens can be minimized by coadministration of antibiotics or hematopoietic growth factors [20,24], which were not used prophylactically in the current study. The incidence of grade 3 or 4 granulocytopenia was probably underestimated in another study in which blood counts were only performed every 3 weeks [18]. The incidence of granulocytopenia was only 41% in a study involving identical dosages of doxorubicin and vinorelbine, possibly because of a slightly lower dose intensity and more delays between cycles [14].…”

“…In our intent-to-treat analysis, the response rate associated with doxorubicin and vinorelbine (55%) appeared to be slightly 274 Vinorelbine with Doxorubicin or Fluorouracil ( (6) 4 (7) 2 (4) lower than that observed in assessable subjects enrolled in four other phase II or III studies using the same regimen (74% and 75%) [14,18] or epirubicin and vinorelbine (70% and 77%) [19,20] as first-line therapy. The median duration of survival in the current study (21 months) was consistent with that in two of the previous studies (18 and 23 months) [18,19] and lower than that in the other two studies (27.5 and 31 months) [14,20]. The response rate (38%) and median survival (13.8 months) were lower when doxorubicin and vinorelbine were evaluated as first-or second-line therapy in a recent Canadian study [21]; outcomes were not specified for first-versus second-line therapy in that study.…”

Epirubicin–vinorelbine vs FEC100 for node-positive, early breast cancer: French Adjuvant Study Group 09 trial

“…Impressive results have been obtained through an every 3-week schedule of vinorelbine 25 mg m À2 , days 1 and 8, plus doxorubicin 50 mg m À2 on day 1, producing an objective response rate of 74% (complete response 21%) and a median survival time of 27.5 months (Spielmann et al, 1994), but at the price of a high level of cardiac toxicity as 10% of patients experienced grades 2 -4 treatment-related cardiotoxicity. In a phase III trial, comparing vinorelbine -doxorubicin and FAC (fluorouracil 500 mg m À2 , doxorubicin 50 mg m À2 and cyclophosphamide 50 mg À2 ), the efficacy of both regimens was similar, whereas vinorelbinedoxorubicin regimen was more active in the subset of patients with visceral metastatic disease, especially liver involvement (Blajman et al, 1999). Giving the better safety profile of epirubicin compared with doxorubicin in terms of haematologic and cardiac toxicities (Torti et al, 1986;Mouridsen, 1990), and the similar efficacy of both anthracyclines when used at equimolar doses of 50 mg m À2 (French Epirubicin Study Group, 1988;Italian Multicentre Breast Study with Epirubicin, 1988), the replacement of doxorubicin by epirubicin could be of interest.…”