Phase III Comparative Study of Vinorelbine Combined With Doxorubicin Versus Doxorubicin Alone in Disseminated Metastatic/Recurrent Breast Cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8

Norris, B.; Pritchard, KI; James, Keith; Myles, James D.; Bennett, Katherine; Marlin, S.; Skillings, Jamey; Findlay, B.; Vandenberg, T.; Goss, Paul E.; Latreille, Jean; Rudinskas, Leona; Lofters, W.; Trudeau, Maureen; Osoba, David; Rodgers, A.

doi:10.1200/jco.2000.18.12.2385

Cited by 132 publications

(67 citation statements)

References 25 publications

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“…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. It is not surprising that fluorouracil and vinorelbine appeared to be associated with a shorter duration of survival (12 versus 21 months) than was doxorubicin and vinorelbine in the current study, given the fact that there were two distinct patient populations treated in this trial.…”

Section: Discussionsupporting

confidence: 79%

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

Hochster

Vogel²,

Burman

et al. 2001

The Oncologist

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Results. For doxorubicin and vinorelbine, the objective response rate was 55% (95% confidence interval [CI]: 42% to 68%), median time to disease progression was 34 weeks, median time to treatment failure was 32 weeks, and median survival was 92 weeks (95% CI: 72 to 128 weeks). For fluorouracil and vinorelbine, the objective response rate was 45% (95% CI: 31% to 59%), median time to disease progression was 32 weeks, median time to treatment failure was 30 weeks, and median survival was 53 weeks (95% CI: 47 to 64 weeks). The most common adverse event was grade 3 or 4 granulocytopenia, which occurred in 95% of subjects in the doxorubicin-vinorelbine group and in 88% of those in the fluorouracilvinorelbine group. The most common nonhematologic adverse event was grade 3 or 4 stomatitis, which occurred in 9% and 32% of subjects in the two groups, respectively.Conclusion. Both vinorelbine-containing regimens appear to offer useful options as initial therapy for advanced breast cancer. Both regimens were active, and any efficacy differences between the two may have been related to differences in prognosis for the anthracyclinepretreated group (i.e., selection for prior aggressive adjuvant therapy) and or comorbid cardiac conditions. Both regimens were associated with predictable but manageable toxicity, but a lower dose of fluorouracil (e.g., 600 mg/m 2 /day) should be used to reduce the risk of stomatitis.

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Section: Discussionsupporting

confidence: 79%

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

Hochster

Vogel²,

Burman

et al. 2001

The Oncologist

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“…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).…”

Section: Discussionsupporting

confidence: 74%

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

Yeh

Hsu

et al. 2005

Br J Cancer

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We prospectively investigated the efficacy and safety of combining weekly vinorelbine (VNB) with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of patients with advanced breast cancer (ABC). Vinorelbine 25 mg m À2 30-min intravenous infusion, and high-dose 5-FU 2600 mg m À2 plus LV 300 mg m À2 24-h intravenous infusion (HDFL regimen) were given on days 1 and 8 every 3 weeks. Between June 1999 and April 2003, 40 patients with histologically confirmed recurrent or metastatic breast cancer were enrolled with a median age of 49 years (range: 36 -68). A total of 25 patients had recurrent ABC, and 15 patients had primary metastatic diseases. The overall response rate for the intent-to-treat group was 70.0% (95% CI: 54 -84%) with eight complete responses and 20 partial responses. All 40 patients were evaluated for survival and toxicities. Among a total of 316 cycles of VNB -HDFL given (average: 7.9: range: 4 -14 cycles per patient), the main toxicity was Gr3/4 leucopenia and Gr3/4 neutropenia in 57 (18.0%) and 120 (38.0%) cycles, respectively. Gr1/2 infection and Gr1/2 stomatitis were noted in five (1.6%) and 59 (18.7%) cycles, respectively. None of the patients developed Gr3/4 stomatitis or Gr3/4 infection. Gr2/3 and Gr1 hand -foot syndrome was noted in two (5.0%) and 23 (57.5%) patients, respectively. Gr1 sensory neuropathy developed in three patients. The median time to progression was 8.0 months (range: 3 -25.5 months), and the median overall survival was 25.0 months with a followup of 5.5 to 45 þ months. This VNB -HDFL regimen is a highly active yet well-tolerated first-line treatment for ABC.

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“…Combining the results of this study with the two published reports DaunoXome has shown objective responses in eight out of 35 (23%) evaluable patients (Anonymous, 1996;Darskaia et al, 1999). The response rate for this relatively non-toxic anthracycline based therapy must be taken in context with those reported for single-agent doxorubicin which vary from 30 -34% in recent randomised phase III studies (Henderson et al, 1989;Sledge et al, 1997;Chan et al, 1999;Norris et al, 2000). The overall time to tumour progression of 5 months (8.5 months in those patients treated at 120 and 150 mg m 2 ) and median survival of 13.75 months are in keeping with the results reported for large randomised studies of doxorubicin when used alone or as part of a combination regimen in the treatment of symptomatic relapsed breast cancer (Norris et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

et al. 2002

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The aims of this phase I study were to establish the maximum tolerated dose, safety profile and activity of liposomal daunorubicin, DaunoXome (NeXstar Pharmaceuticals), in the treatment of metastatic breast cancer. DaunoXome was administered intravenously over 2 h in 21 day cycles and doses were increased from 80 to 100, 120 and 150 mg m 2 . Sixteen patients were enrolled. A total of 70 cycles of DaunoXome were administered. The maximum tolerated dose was 120 mg m 2 , the dose-limiting toxicity being prolonged grade 4 neutropenia or neutropenic pyrexia necessitating dose reductions at 120 and 150 mg m 2 . Asymptomatic cardiotoxicity was observed in three patients: grade 1 in one treated with a cumulative dose of 800 mg m 2 and grade 2 in two, one who received a cumulative dose of 960 mg m 2 and the other a cumulative dose of 600 mg m 2 with a previous neoadjuvant doxorubicin chemotherapy of 300 mg m 2 . Tumour response was evaluable in 15 patients, of whom two had objective responses, six had stable disease and seven had progressive disease. In conclusion, DaunoXome is associated with mild, manageable toxicities and has anti-tumour activity in metastatic breast cancer. The findings support further phase II evaluation of DaunoXome alone and in combination with other standard nonanthracycline cytotoxic or novel targeted agents. Although the dose-limiting toxicity for DaunoXome was febrile neutropenia at 120 mg m 2 , we would recommend this dose for further evaluation, as the febrile neutropenia occurred after four or more cycles in three of the four episodes seen, was short lived and uncomplicated.

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Phase III Comparative Study of Vinorelbine Combined With Doxorubicin Versus Doxorubicin Alone in Disseminated Metastatic/Recurrent Breast Cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8

Abstract: The survival with DOX and VNB is not superior to DOX alone in MBC.

Cited by 132 publications

References 25 publications

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

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

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

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

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