Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC 409962) and cyclophosphamide therapy of drug-resistant metastatic breast carcinoma

Presant, Cary A.; Amburg, Albert Van; Klahr, Carol

doi:10.1002/1097-0142(197709)40:3<987::aid-cncr2820400304>3.0.co;2-0

Cited by 13 publications

(2 citation statements)

References 6 publications

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“…The drugs are usually chosen for such combinations for the following reasons: (a) they kill cells in different parts of the cell cycle; (b) they do not have overlaping toxicities in normal tissues; (c) their combined effects are synergistic; (d) the individual drugs (used alone) are very effective against a particular tumor; (e) the drugs are schedule dependent (14,16,(32)(33)(34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous responses of an in vitro model of human stomach cancer to anticancer drugs

et al. 1983

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Four permanent clones of a human adenocarcinoma of the stomach and the parent line from which they were isolated were used as an in vitro model system to evaluate the effects of 8 anticancer agents on cell survival. The drugs tested were actinomycin D (Act-D), Bleomycin (Bleo), adriamycin (adria), melphalan, chlorambucil, 5 Fluorouracil (5FU), 1,2:5,6-Dianhydrogalactitol (DAG), and 1-(2-chloroethyl)-3-(4-methyl cyclohexyl-1-nitrosourea) (MeCCNU). Although the cell lines had similar growth properties, morphologies and modal chromosome numbers, the clones expressed heterogeneous survival responses to each of six drugs tested. A comparison of the doses lethal to 90% of a clonal population (LD90) for each drug indicated large differences between the most sensitive and least sensitive clones. For chlorambucil there was a 160% difference between the LD90 values of the most and least sensitive clones. For MeCCNU the difference was 200%; for adria, 230%; Bleo, 280%; 5FU, 360%; and melphalan, 600%. Despite the heterogeneity in response among the clones to these agents, no particular clone was always the most sensitive or resistant. Of particular interest was the finding that these stomach cancer clones demonstrated uniform responses to both Act-D and DAG. Since the differential drug sensitivities expressed by heterogeneous tumor populations could be a cause of treatment failure in the patient, the demonstration of uniform sensitivities to Act-D and DAG are encouraging and suggest that other anticancer drugs which produce uniform cell killing may be identified and tested. Act-D and adria were the most effective of the drugs tested when compared on a dose for dose basis. Both agents killed more than 99.9% of the parent cell line with doses below 3 micrograms/ml (1-h treatments). The cells were least sensitive to 5FU, with only 30% of the cells killed at 100 micrograms/ml. The studies reported here indicate that this human stomach cancer model can provide valuable insight into the design of clinical protocols for treatment of gastric carcinoma in man.

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Section: Discussionmentioning

confidence: 99%

Heterogeneous responses of an in vitro model of human stomach cancer to anticancer drugs

et al. 1983

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“…12 Previous ECOG studies have shown that the addition of Halotestin to CMF maintenance results in longer time to treatment failure. l 3 The combination of dibromodulcitol, Adriamycin, vincristine, tamoxifen, and Halotestin (DAVTH) was piloted at the University of Pretoria (Pretoria, South Africa) and the University of Wisconsin (Madison, WI) with complete and partial responses in 15 of 20 patients within the first 3 months of treatment. 14 Based upon these observations of the effectiveness of both the thiotepa-based regimen and the dibromodulcitolbased regimen, the benefit of Halotestin in giving longer time to treatment failure, the necessity for developing a program for patients who had previously been treated with tamoxifen, and the desirability of having a regimen that would be effective in patients previously treated with CMF, the combination dibromodulcitol, Adriamycin, vincristine, and Halotestin (DAVH) was selected for comparison with TAVH.…”

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Combination chemotherapy of advanced breast cancer. Comparison of dibromodulcitol, doxorubicin, vincristine, and fluoxymesterone to thiotepa, doxorubicin, vinblastine, and fluoxymesterone: An eastern cooperative oncology group study

Skeel¹,

Andersen²,

Tormey³

et al. 1989

Cancer

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Two Adriamycin (doxorubicin)-based chemotherapy regimens were investigated in patients with carcinoma of the breast who had failed prior systemic therapy. The two chemotherapy programs, dibromodulcitol, Adriamycin, vincristine, and Halotestin (fluoxymesterone) (DAVH), and thiotepa, Adriamycin, vinblastine, and Halotestin (TAVH), were chosen for comparison on the basis of reported response rates of 40% to 50% with remission durations of 11 months in patients refractory to other cytotoxic chemotherapy. Cycles of DAVH were repeated every 4 weeks. Cycles of TAVH were repeated every 3 weeks. Of 184 patients evaluable for response, 32% of patients treated with DAVH and 38% of patients treated with TAVH had a complete response (CR) or partial response (PR). An additional 5% of patients had nonmeasurable improvement in osseous disease for an overall rate of response (CR + PR + improvement) of 40%. Patients who had previously received cytotoxic chemotherapy for metastatic disease or had early failure after adjuvant therapy had a lower response rate to DAVH, but not to TAVH than those who did not fail prior chemotherapy. Duration of response and survival were similar with the two treatments. There were seven treatment-related deaths, five among patients receiving DAVH and two among patients receiving TAVH. Patients receiving DAVH had significantly more thrombocytopenia and neurologic toxicity than those receiving TAVH. These treatments appear to be reasonable second-line regimens and are good candidates to be used in initial therapy of metastatic disease or adjuvant therapy studies that explore the use of alternating non-cross-resistant combinations with cyclophosphamide, methotrexate, and 5-fluorouracil.

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Vinblastine, adriamycin, thiotepa, and halotestin (VATH). Therapy for advanced breast cancer refractory to prior chemotherapy

Perloff¹,

Hart²,

Holland³

1978

Cancer

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Nineteen postmenopausal patients with metastatic breast cancer refractory to conventional combination chemotherapy were treated with monthly cycles with the combination of vinblastine, adriamycin, thiotepa and halotestin. Ten patients (52%) responded with a greater than 50% regression of measurable tumor. The median duration of response was 11.5 months, with 5/10 patients still responding at a mean follow-up of 10 months. Only 2/10 responders have died with a mean follow-up of 13.8 months. In contrast, 8/9 nonresponders have died (median survival 6.0 months). Response to therapy was neither influenced by site of disease, time interval from diagnosis to primary chemotherapy nor duration of response to primary chemotherapy. No patient was hospitalized because of drug induced toxicity. This combination of drugs is a tolerable effective regimen for patients relapsing after adjuvant chemotherapy or after primary combination chemotherapy for grossly metastatic disease.

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Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC 409962) and cyclophosphamide therapy of drug-resistant metastatic breast carcinoma

Cited by 13 publications

References 6 publications

Heterogeneous responses of an in vitro model of human stomach cancer to anticancer drugs

Heterogeneous responses of an in vitro model of human stomach cancer to anticancer drugs

Combination chemotherapy of advanced breast cancer. Comparison of dibromodulcitol, doxorubicin, vincristine, and fluoxymesterone to thiotepa, doxorubicin, vinblastine, and fluoxymesterone: An eastern cooperative oncology group study

Vinblastine, adriamycin, thiotepa, and halotestin (VATH). Therapy for advanced breast cancer refractory to prior chemotherapy

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