Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU-NSC 409462), and cyclophosphamide in refractory adenocarcinoma of the breast and other tumors

Presant, Cary A.; Kolhouse, J F; Klahr, Carol

doi:10.1002/1097-0142(197602)37:2<620::aid-cncr2820370203>3.0.co;2-d

Cited by 13 publications

(2 citation statements)

References 5 publications

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“…It is still doubtful whether and how carcinogenetic data recorded under experimental conditions in animals can quantitatively be extrapolated to the human situation. However, in contrast to common long-term bioassays in rodents that are carried out to identify cancer-causing chemicals in the environment, the doses used in the present experiment are below the actual burden in humans (Preussmann, 1975).…”

Section: Discussionmentioning

confidence: 98%

Carcinogenic action of low‐dose cyclophosphamide given orally to sprague‐dawley rats in a lifetime experiment

Schmähl

1979

Intl Journal of Cancer

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In a lifelong experiment Sprague-Dawley rats received cyclophosphamide (CP) i n drinking water. Daily doses of 2.5 (I). 1.25 (II), 0.63 (Ill), and 0.31 (IV) mg/kg body weight were given t o groups of 40 male and 40 female rats five times a week. The median survival time (MST) of treated rats proved to be dose-dependent. In rats treated with dose I the MST was 638 days for males and 642 for females, i n those given dose IV it was 906 days for males and 934 days for females. The percentage of control animals with malignant tumors was 11% for males and 15% for females. The corresponding figures for CP-treated animals ranged from 32 t o 43% for male rats and from 30 t o 35% for females. A t doses I, II, and 111 CP proved t o be carcinogenic (p vs control<0.05). No carcinomas of the urinary bladder were found i n controls but one female showed a benign papilloma of the bladder. However, 17 CP-treated rats died with carcinomas of the urinary bladder and, remarkably, only one of these was a female. In addition, 18 male and 10 female animals showed benign tumors of the same organotropy. No leukemia was diagnosed in controls, but in CP-treated rats leukemia was found in 8 male and 11 female animals. These findings support the evidence emerging from case reports in humans showing an increased risk of cancer of the urinary bladder as well as of leukemia i n patients treated with CP.

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Section: Discussionmentioning

confidence: 98%

Carcinogenic action of low‐dose cyclophosphamide given orally to sprague‐dawley rats in a lifetime experiment

Schmähl

1979

Intl Journal of Cancer

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“…Such Gly-I inactivation may then help overcome drug resistance, leading to growth cessation and/or cell death in prostatic cancer cells. Moreover, clinical trials of BCNU on patients with PC were conducted more than 20 years ago (Presant et al, 1976(Presant et al, , 1980, and showed some promising outcomes. However, because no further studies have been reported since then, it is worthwhile to resume the investigation of BCNU to reevaluate its efficacy on prostatic cancer cells and to explore its cytotoxic mechanism.…”

Section: Introductionmentioning

confidence: 99%

Chemosensitization of Carmustine with Maitake β-Glucan on Androgen-Independent Prostatic Cancer Cells: Involvement of Glyoxalase I

Finkelstein

Aynehchi

Samadi

et al. 2002

The Journal of Alternative and Complementary Medicine

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Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC 409962), cyclophosphamide plus prednisone (ABC-P) in melphalan-resistant multiple myeloma

Presant

Klahr

1978

Cancer

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Fourteen patients with multiple myeloma resistant to melphalan plus prednisone were treated with BCNU 50 mg/m2 plus cyclophosphamide 200 mg/m2 on day 1, adriamycin 20 mg/m2 on day 2 and prednisone 60 mg orally, daily for days 1 through 5. Therapy was repeated every four weeks. Depending upon criteria used, objective antitumor responses were achieved in five to nine of the 14 patients. Mean survival was 9.5 months and actuarial median survival was 7.0 months. Six patients are alive, four to 35 months after initiation of therapy. This preliminary report indicates that this combination may be a useful treatment program in the management of patients with advanced multiple myeloma. A review of studies employing adriamycin plus BCNU s u g gests that these regimens currently offer the most effective treatment of melphalan-resistant patients.Cancer 42:1222-1227, 1978.DIFFICULT MANAGEMENT problem facing A the physician is the therapy of patients with multiple myeloma which has become refractory to treatment with melphalan plus prednisone, the initial standard therapy in most institutions. During a Phase I1 evaluation of a combination of adriamycin, BCNU, plus cyc1ophosphamide,l0 encouraging results were observed in several patients with multiple myeloma treated with these three drugs plus prednisone (ABC-P). Study of the regimen has continued, and this preliminary report details the pretreatment characteristics of the patients, the therapeutic and toxic effects of the drugs, and the responses observed. ABC-P appears to be an effective treatment program for patients with melphalan-resistant multiple myeloma. MATERIALS AND METHODSPatients were eligible for this treatment program if they had multiple myeloma diagnosed by the criteria of the Multiple Myeloma Task Force,5 and had shown progression of disease while receiving melphalan plus prednisone, with or without additional chemotherapy. Progression of disease was established by a greater than 25% increase in M-protein concentration or daily M-protein excretion rate, by progression of bone lesions as evaluated by radiological techniques, or by a greater than 50% increase in the sum of the products of the perpendicular diameters of plasmacytomas. No patients were excluded for low performance status, and no patients were excluded due to any type of prior chemotherapy.Patients with myeloma were treated with a combination of BCNU, 50 mg/m2 administered over 30 minutes intravenously, followed immediately by cyclophosphamide, 200 mg/ m2 as a bolus injection, and followed in 18 to 24 hours by adriamycin, 20 mg/m2 as a bolus injection. At the initiation of therapy, patients were begun on prednisone, 60 mg orally, daily for five days. Therapy was repeated every four weeks, and dose adjustments were made as previously described.1°Pretreatment and monthly evaluations included weight, physical examination, deter-

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Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU-NSC 409462), and cyclophosphamide in refractory adenocarcinoma of the breast and other tumors

Cited by 13 publications

References 5 publications

Carcinogenic action of low‐dose cyclophosphamide given orally to sprague‐dawley rats in a lifetime experiment

Carcinogenic action of low‐dose cyclophosphamide given orally to sprague‐dawley rats in a lifetime experiment

Chemosensitization of Carmustine with Maitake β-Glucan on Androgen-Independent Prostatic Cancer Cells: Involvement of Glyoxalase I

Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC 409962), cyclophosphamide plus prednisone (ABC-P) in melphalan-resistant multiple myeloma

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