Combination chemotherapy (VAC/FMC) with immunostimulation in metastatic breast cancer: A randomized study comparing different times and routes of administration of corynebacterium parvum

Abstract

From January 1978 to December 1980, 222 patients with metastatic breast cancer were included into a prospective multicenter trial. All patients were treated once a month with six cycles of VAC- (vincristine, adriamycin, cyclophosphamide) chemotherapy, followed by FMC (5-fluorouracil, methotrexate, cyclophosphamide) until progression was documented. By random assignment, the patients received immunostimulation with Corynebacterium parvum (CP) by one of four methods: subcutaneous (SC) on either day 1 or day 14, intravenous (IV) on either day 1 or day 14. The 214 evaluable patients were equally distributed to the four arms. The rates of complete or partial response to VAC/FMC plus CP did not differ significantly between the treatment groups. Of our patients, 22-33% were definite treatment failures. The Kaplan-Meier curves of duration of remission (medians 14 vs. 9 vs. 13 vs. 11 months) did not differ significantly. Only small differences in survival were noted among the four study groups (medians 15.4 vs. 17.5 vs. 17.2 vs. 13.0 months). However, complete and partial responders lived significantly longer (Log rank test P = 0.008), when CP was given on day 14 by the SC rather than IV route (29+ vs. 14.3 months). Patients in the four study groups were treated with virtually identical doses of VAC/FMC chemotherapy. Patients receiving CP intravenously on day 14 experienced significantly lower mean leukocyte counts than patients in the other groups. Many patients suffered from high temperature (requiring treatment with antipyretics) and severe gastrointestinal toxicity, particularly when CP was given IV on day 1 together with the chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective Randomized Trial Concerning Hyper- and Normoprolactinemia and the Use of Bromoergocryptine in Patients with Metastatic Breast Cancer

“…Over 50% of the hyperprolactinemics (16/31) and normoprolactinemic 'high risks* (25/43) have died com pared to 4 of 13 'low risks'. Median survival of all patients ('overall survival') was 14 months, which is 4 weeks less than in both previous studies [4,5).…”

“…According to SAKK criteria already used in our previous studies [4,5], complete remission (CR) was defined as the disappearance of all …”

“…However, recent results of treatment with combination chemotherapy suggest a plateauing of success such that some 50-70% of patients may be expected to respond to current first-line combination che motherapy with a median duration of response of 9-14 months and a median survival of 2 years [4,5]. The disappointing inability to further improve on these results (including an overall survival of 15-18 months) with changes in type, dose, number, or scheduling of cytotoxic drugs has led us to reconsider the influence of various prognostic factors in metastatic breast cancer.…”

History of Immunotherapy – from Coley Toxins to Checkpoints of the Immune Reaction

“…První úspěšné klinické pokusy, de facto navazující na původní Coleyovu myšlenku o imunoterapii nádorů s pomocí infekčních agens, byly publikovány v polovině 70. a začátkem 80. let minulého století. Pa cientům, kteří trpěli různými nádory, na počátku zejména těm s karcinomem prsu, byla podávána živá bacillus Calmette-Guerin (BCG) vakcina [10] nebo Corynebacterium parvum [11]. Dnes je BCG terapie vyhrazena pro intravezikální aplikaci pa cientům s povrchovými lézemi karcinomu močového měchýře.…”

Immunotherapy of breast cancer: A review of the development of cell‐specific therapy

“…Another series of studies has utilized Corynebacterium parvum as an immunostimulant to both the cell-mediated immune system, as well as to the macrophage systenm [57]. When given with adjuvant chemotherapy, C. parvum does not appear to benefit cancer patients, and is associated with significant toxicity, including hyperpyrexia, gastrointestinal complaints, and skin ulceration [58]. Corynebacterium granulosum, or P40, has also been used in therapy.…”