Adjuvant Chemoimmunotherapy with LMF + BCG in Node-Negative and Node-Positive Breast Cancer: 8 Year Results

Hj, Senn; Wf, Jungi; Amgwerd, R; Hochuli, E; Ammann, Johannes; Engelhart, G. J.; Heinz, C; Wick, A; Enderlin, F; Creux, G

doi:10.1007/978-3-642-82357-2_11

Cited by 9 publications

(3 citation statements)

References 9 publications

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“…In a retrospective study on patients included in a randomized trial of adjuvant chemotherapy on nodepositive breast cancer, Bonadonna and Valagussa (1981) demonstrated a significant correlation between unscheduled dose reduction and reduced survival. Similar results have been published subsequently from many retrospective studies in early and advanced breast cancer (Rodriguez-Kraul et al, 1981;Tormey et al, 1983;Howell et al, 1984;Senn et al, 1984;Ang et al, 1989;Pronzato et al, 1989), however some retrospective studies have failed to demonstrate any significant correlation between dose and therapy efficacy (Ahmann et al, 1982;Glucksberg et al, 1982;Redmond et al, 1983;Mouridsen et al, 1984;Velez-Garcia et al, 1987). A series of analyses on published chemotherapy studies demonstrated that a positive correlation existed between the scheduled amount of drug per unit time and the efficacy of chemotherapy treatment on both early and advanced breast cancer (Hryniuk and Bush, 1984;Hryniuk and Levine, 1986).…”

supporting

confidence: 87%

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer

Saarto

Blomqvist²,

Rissanen³

et al. 1997

Br J Cancer

123

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Summary Two hundred and eleven patients with node-positive stage 11 and IlIl breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (Dl), dose intensity of the two initial cycles (Dl2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P=0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy.

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supporting

confidence: 87%

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer

Saarto

Blomqvist²,

Rissanen³

et al. 1997

Br J Cancer

123

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“…Bonadonna and Valgussa found in 1981 that disease-free survival was shorter in node-positive breast cancer patients who received a reduced dose of adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) than in those who received full or nearly full dose (Bonadonna and Valagussa, 1981) Similar findings have been published in other retrospective studies in early and advanced breast cancer (Rodriguez et al, 1981;Tormey et al, 1983;Howell et al, 1984;Senn et al, 1984;Ang et al, 1989;Pronzato et al, 1989) while in some studies no significant correlation between the given dose and survival benefit was found (Ahmann et al, 1982;Glucksberg et al, 1982;Redmond et al, 1983;Mouridsen et al, 1984;Velez-Garcia et al, 1987). These studies have been criticized due to the bias inherent in this kind of retrospective analysis (Redmond et al, 1983).…”

mentioning

confidence: 55%

Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF

Poikonen

Saarto

Lundin³

et al. 1999

Br J Cancer

103

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SummaryThe purpose of this study was to examine the association between the leucocyte nadir and prognosis in breast cancer patients receiving adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF). Three hundred and sixty-eight patients with node-positive breast cancer without distant metastases were treated with six cycles of adjuvant CMF. Some patients (n = 60) also received tamoxifen. All patients underwent surgery and received radiotherapy to the axillary and supraclavicular lymph nodes and the chest wall. The effect of leucopenia caused by CMF on distant disease-free survival (DDFS) and overall survival (OS) was assessed. A low leucocyte nadir during the chemotherapy was associated with a long DDFS in univariate analysis when tested as a continuous variable (the relative risk (RR) 1.3, 95% confidence interval (CI) 1.04-1.06, P = 0.02). Similarly, when the leucocyte nadir count was divided into tertiles, the patients who had the highest nadir values during the six-cycle treatment had worst outcome (RR 1.6, 95% CI 1.07-2.5, P = 0.02). However, in a multivariate analysis only the number of affected lymph nodes, tumour size, progesterone receptor status, surgical procedure, age and adjuvant tamoxifen therapy retained prognostic significance, whereas the leucocyte nadir count did not. A low leucocyte nadir during the adjuvant CMF chemotherapy is associated with favourable DDFS and it may be a useful biological marker for chemotherapy efficacy.

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“…Two trials [9,23] have utilized only single-agent chemotherapy with L-PAM, which is not considered today to represent an adequate treatment in the presence of advanced disease as well as in an adjuvant situation [24,25]. As far as the route of drug administration is concerned, 3 trials [9,23,26] have utilized only the oral administration of cytotoxic compounds. The inconsistency of intestinal absorption and drug compliance is well known.…”

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confidence: 99%

Adjuvant chemotherapy in postmenopausal women: Results of sequential noncross‐resistant regimens

et al. 1985

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This article reports the 6-year results of a controlled adjuvant trial carried out in 140 postmenopausal women aged 65 years or less having resectable breast cancer and positive axillary nodes. Within 4 weeks after surgery, patients were started on cyclophosphamide, methotrexate, and fluorouracil and prednisone (CMFP) for 6 cycles foilowed by Adriamycin | plus vincristine (AV) for 4 cycles. Chemotherapy was delivered with minimal dose reduction schedule. Patients were randomized to receive standard dose regimen for both combinations (treatment A) or progressive dose intensification (treatment B). There was no significant difference in the relapse-free (RFS) and overall survival (OS) rates between the 2 treatment groups. Treatment results were inversely related to the number of involved axillary nodes. In the subset with 1 to 3 positive nodes, present findings are superior (RFS 75.2%, OS 84.2 %) when retrospectively compared to the 6-year results achieved with adjuvant CMF in the same postmenopausal subset (12 cycles: RFS 55.4%, OS 67.3%; 6 cycles: RFS 47.5%, OS 65.5%). Acute toxicity was moderate and reversible, and no patient showed signs of cardiomyopathy. The results of this trial indicate that sequential noncrossresistant combinations administered with minimal dose reductions can favorably affect the postoperative course of postmenopausal women with limited nodal involvement. The study design does not allow for quantitating the relative contribution of CMFP versus AV chemotherapy.

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Adjuvant Chemoimmunotherapy with LMF + BCG in Node-Negative and Node-Positive Breast Cancer: 8 Year Results

Cited by 9 publications

References 9 publications

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer

Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF

Adjuvant chemotherapy in postmenopausal women: Results of sequential noncross‐resistant regimens

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