Effective treatment of advanced breast cancer with vinorelbine, mitomycin C plus human granulocyte colony-stimulating factor

Abstract

Summary A phase II trial was performed to evaluate the efficacy and tolerance of vinorelbine (VNB), mitomycin C (MMC), and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between October 1992 and July 1994, 55 patients entered this trial. Nine patients had locally advanced disease and 46 had distant metastases, including 14 who had received previous palliative chemotherapy with (n = 9) or without anthracyclines (n = 5). Therapy consisted of VNB 40 -50 mg m-2 diluted in 250 ml saline infused over 30 min every 3 weeks, and MMC 15 mg m-2 administered by intravenous bolus injection every 6 weeks. G-CSF was given at 5 pg kg-' day-' subcutaneously from days 2 to 7 following each cytotoxic drug administration. Treatment was continued in case of response or stable disease for a total of six courses. The overall response rate was 73% for all 55 patients (95% confidence interval, 59-84%), including 12 (22%) complete response (CR) and 28 (51 %) partial response (PR); 13 patients (24%) had stable disease (SD), and only two (4%) progressed. All nine patients with locally advanced disease were rated responsive (two pCR, seven PR) and underwent surgery with curative intent. Eight out of nine remain disease free after a median observation period of 18 months (range, 13.5-28 months). Among the 32 previously untreated patients with metastatic disease, nine (28%) achieved CR, 15 PR (47%), seven SD (22%) and one PD (3%). Second-line chemotherapy with this regimen resulted in 7/14 (50%) objective remissions (one CR, six PR), six had SD and one PD. The median time to progression was 12 months (range, 2-24+months) in previously untreated patients with disseminated disease, and 6.0 months (range, 2 -22 months) in those who had failed prior chemotherapy. After a median follow-up time of 20 months, 24 patients with distant metastases are still alive with disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: six (11 %) and ten patients (18%) had World Health Organization grade 3, and eight (14%) and nine patients (16%) had grade 4 leucopenia and granulocytopenia respectively. Severe (WHO grade 3) non-haematological toxicities included nausea/ vomiting in 7%, constipation in 9%, peripheral neuropathy in 5%, infectious episodes in 7%, phlebitis due to drug extravasation in 5%, alopecia in 9%, and acute reversible pulmonary toxicity in 11 %. Our data suggest that vinorelbine, mitomycin C plus G-CSF has an excellent anti-tumour activity in advanced breast cancer, probably superior to most other available combination chemotherapy regimens. This combination does not seem to present significant cross-resistance with previous CMF or anthracycline regimens. Apart from reversible, acute pulmonary toxicity, a rare adverse reaction that had previously been described for VNB, as well as the combination of natural vinca alkaloids with mitomycin C, and few episodes of grade 3 neurotoxicity (all of which occurred at the initial 50 mg m 2 VNB dose level), the toleranc...

Effective treatment of advanced breast cancer with vinorelbine, 5-fluorouracil and l-leucovorin plus human granulocyte colony-stimulating factor

“…a substantial activity for combination regimens including this agent would be anticipated. and preliminary results seem to confirm these expectations (Scheithauer et al 1993: Spielmann et al 1994: Fabi et al 1995: Nole et al 1995: Kornek et al 1996.…”

“…substantial activity for combination regimens including this agent would be anticipated. Among several such combination regimens that have alreadv been investigated in patients with advanced breast cancer (Scheithauer et al 1993: Spielmann et al 1994: Fabi et al 1995: Nole et al 1995: Kornek et al 1996. the combination of vinorelbine and doxorubicin has probably shown the most promising activitv: there was a relatively hiah rate of cardiotoxicitv (10%7) however.…”

“…prior therapy must have been completed at least 4 weeks before study entry with full resolution of toxicities. may be alleviated by prophylactic use of a haematopoietic growth factor such as G-CSF, the present study was initiated Compared with previous, encouraging pilot studies of this drug combination (Lopirinzi et al, 1989;Swan et al, 1989;Margolin, 1992;Scheithauer et al, 1993;Nole et al, 1995;Kornek et al, 1996), we have used full chemotherapeutic drug doses of vinorelbine and 5-FU. In addition, instead of racemic leucovorin (LV).…”

Vinorelbine + Mitomycin C as Second-Line Treatment of Metastatic Breast Cancer: A Two-Stage Phase 2 Study

“…Similarly, also in the light of the report by Kornek et al [16]of a response rate with VM in first-line treatment exceeding 70%, VM could be proposed as a reasonable schedule for first-line chemotherapy of patients relapsing after the use of anthracyclines and taxanes as neoadjuvant or adjuvant treatment. However, to support this proposal, further studies testing the activity of VM in patients previously treated with taxanes would be useful.…”

Vinorelbine and Carboplatin in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

“…These observation led to the suggestion that VNR might be less neurotoxic and more toxic to the cancer cell. During the past 6 years, VNR has undergone extensive clinical evaluation and has shown activity in a number of malignancies including breast cancer [5] and non-small cell lung cancer [6,7]. Based on these results, the potential synergistic activity of VNR and carboplatin and promising results of the combination of cisplatin and VNR in HNSCC [8,9], we have initiated this phase II trial.…”