A phase II trial of vinorelbine and thiotepa in metastatic breast cancer

Fabi, Alessandra; Tonachella, R; Savarese, Antonella; Cirulli, S.; Tomao, Silverio; Conte, Esmeralda; Cognetti, F.

doi:10.1093/oxfordjournals.annonc.a059115

Cited by 12 publications

(9 citation statements)

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“…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.…”

supporting

confidence: 57%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Kornek

Haider²,

Kwasny³

et al. 1998

Br J Cancer

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Summary A phase 11 trial was performed to investigate the efficacy and tolerance of vinorelbine (VNB), 5-fluorouracil (5-FU), I-leucovorin (LLV) and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between August 1994 and October 1996, 53 patients entered this trial. Thirty-seven patients were previously untreated and 16 patients had failed previous palliative chemotherapy with (n = 12) or without anthracyclines (n = 4). Therapy consisted of VNB 40 mg m-2 diluted in 250 ml of saline infused over 30 min on days 1 and 14 and LLV 100 mg m-2 administered by intravenous bolus injection and 5-FU 400 mg m-2 diluted in 500 ml of saline infused over 2 h, both given on days 1-5 every 4 weeks. G-CSF was administered at 5 9g kg-' day-' subcutaneously on days 6-10 during each cycle. Treatment was continued in cases of response or stable disease until a total of six courses were completed. The overall response rate was 59% for chemotherapeutically naive patients (95% confidence interval 42-75%), including five complete responses (CR; 13%) and 17 partial responses (PR; 46%); ten patients (27%/6) had stable disease (SD) and only five (14%) progressed (PD). Second-line chemotherapy with this regimen resulted in 3/16 (19%) objective remissions, but nine patients had SD and four had PD. The median time to progression was 10.5 months (range 2-23) in previously untreated patients and 7.0 months (range 2-19) in those who had failed prior chemotherapy. After a median follow-up time of 14 months, 29 patients (55%) are still alive with metastatic disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: WHO grade IlIl and IV neutropenia occurred in 15 (28%) and four patients (8%), and was complicated by septicaemia in two; grade IlIl anaemia and thrombocytopenia were noted in four (8%) and three (6%) patients respectively. Severe (WHO grade 3) non-haematological toxicitles included stomatitis in 6% and nausea/vomiting and alopecia in 2% each. Our data suggest that the combination of vinorelbine, 5-fluorouracil and 1-leucovorin plus G-CSF is an effective first line regimen for treatment of advanced breast cancer. Overall toxicity was modest, with myelosuppression being the dose-limiting side-effect. Other severe adverse reactions were uncommon.

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supporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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

Kornek

Haider²,

Kwasny³

et al. 1998

Br J Cancer

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“…In all of these studies, treatment was well tolerated, with neutropenia being the most frequent and dose-limiting toxicity. Based on these results and documented activity of single-agent vinorelbine in second-line chemotherapy (Gasparini et al, 1994;Degardin et al, 1994), a substantial activity for combination regimens including this agent would be anticipated, and preliminary results seem to confirm these expectations (Spielmann et al, 1994;Fabi et al, 1995;Nole et al, 1995).…”

mentioning

confidence: 82%

“…(Cannabbio et al, 1989;Garcia-Conde et al, 1992;Romero et al, 1994;Toussaint et al, 1994;Fumoleau et al, 1994), substantial activity for combination chemotherapy including this agent would be anticipated. Among several different such combination regimens that have been investigated in advanced breast cancer (Spielmann et al, 1994;Fabi et al, 1995;Nole et al, 1995), the combination of vinorelbine and doxorubicin has shown the most promising activity, although there was a relative high rate of cardiotoxicity (10%) resulting in three (4%) treatmentassociated toxic deaths (Spielmann et al, 1994).…”

Section: Survivalmentioning

confidence: 99%

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

Kornek

Haider²,

Kwasny³

et al. 1996

Br J Cancer

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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...

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“…Efficacy and tolerance of vinorelbine were investigated in patients with metastatic breast carcinoma (MBC), with encouraging results, in several studies of first-or secondline therapy alone [1][2][3], and in combination with other drugs [4][5][6]. The effectiveness of 5-fluorouracil (5FU) in adenocarcinomas is well known [7].…”

mentioning

confidence: 99%

Phase II Trial of Navelbine and Fluorouracil as Second-Line Chemotherapy in Metastatic Breast Carcinoma

Froudarakis¹,

Catimel²,

Guastalla³

et al. 1997

Oncology

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Vinorelbine [Navelbine^® (NVB); Fabre, Castres, France] is a semisynthetic vinca alkaloid. Efficacy and tolerance of vinorelbine were investigated in patients with metastatic breast carcinoma (MBC), with encouraging results, in several studies of first- or second-line therapy alone [1–3], and in combination with other drugs [4–6]. The effectiveness of 5-fluorouracil (5FU) in adenocarcinomas is well known [7]. Based on these results, we initiated a phase II trial of an NVB and 5FU combination in patients with MBC [8]. The aim was to explore the effectiveness and toxicity of this combination.

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A phase II trial of vinorelbine and thiotepa in metastatic breast cancer

Abstract: The present study has shown this combination to be active as second-line treatment, and its toxic effects have been well tolerated. It should be considered a reasonable option for patients with metastatic disease who have already been treated with anthracyclines.

Cited by 12 publications

References 1 publication

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

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

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

Phase II Trial of Navelbine and Fluorouracil as Second-Line Chemotherapy in Metastatic Breast Carcinoma

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