melphalan and Carcinoma--Intraductal--Noninfiltrating

Topics: Adenocarcinoma, Mucinous; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leukopenia; Lymphatic Metastasis; Mastectomy; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prospective Studies; Thrombocytopenia

Conventionally in vitro cytotoxicity assays are performed as single-end-point determinations. To compensate for the diversity of growth rates among different cell lines in this report we describe a computerized kinetic chemosensitivity assay based on quantification of biomass by staining cells with crystal violet. As a prerequisite four human breast cancer cell lines (MDA-MB-231, MCF-7, T-47-D and ZR-75-1) were characterized with regard to oestrogen and progesterone receptor content, modal chromosome number and proliferation kinetics depending on the number of passages in culture. With prolonged time in culture for ZR-75-1 exposed to various concentrations of cisplatinum a dose-related increase in drug effect was observed. Owing to a correction of the T/C values for the initial cell mass (at the time when drug is added) a sharp distinction between cytostatic and cytocidal drug effects becomes obvious in plots of corrected T/C values versus time of incubation. The influence of the untreated control on the corrected T/C values and possible time courses of theoretical inhibition profiles (reflecting cytostatic, transient cytotoxic or cytocidal drug effects as well as development of resistance) and their relationship to the corresponding growth curves of drug-treated cells are discussed. Chemosensitivity assays with diethylstilbestrol dipropionate, tamoxifen, melphalan, cisplatinum, vinblastine, Adriamycin and 5-fluorouracil prove the theoretical considerations to be true for MDA-MB-231, MCF-7, T-47-D and ZR-75-1 human breast cancer cell lines in practice.

Topics: Adenocarcinoma; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cell Division; Cisplatin; Diethylstilbestrol; Drug Screening Assays, Antitumor; Female; Fluorouracil; Gentian Violet; Humans; Kinetics; Melphalan; Neoplasms, Hormone-Dependent; Receptors, Estrogen; Receptors, Progesterone; Tumor Cells, Cultured; Vinblastine

The clinical and pathologic findings in a 53-year-old woman who developed a uterine adenosarcoma following an adenomyoma are described. During the interval between the diagnosis of adenomyoma and the subsequent diagnosis of adenosarcoma, the patient developed breast carcinoma and received adjuvant chemotherapy that included tamoxifen. The possible stimulatory effects of this drug upon the patient's pre-existing adenomyoma are discussed in view of reports of tamoxifen-associated endometrial carcinoma and uterine sarcomas developing in the setting of estrogen excess.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cell Transformation, Neoplastic; Combined Modality Therapy; Doxorubicin; Endometriosis; Female; Fluorouracil; Humans; Melphalan; Menopause; Middle Aged; Tamoxifen; Uterine Neoplasms; Wilms Tumor

Alkalating chemotherapeutic agents are frequently implicated in the development of acute non-lymphocytic leukemia. A case report illustrates the danger of administering a prolonged course of adjuvant chemotherapy with Melphalan following mastectomy for breast cancer.

Topics: Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Chromosome Deletion; Chromosomes, Human, Pair 7; Female; Humans; Leukemia, Myelomonocytic, Acute; Melphalan; Middle Aged; Risk Factors; Time Factors

We compared the effects of defined medium, fetal bovine serum (FBS) and human serum (HuS) on the growth and responses to chemotherapeutic agents of human breast cancer cells in primary culture. Normal and tumor tissues were dissociated to small aggregates and single cells and seeded onto collagen-gel-coated wells in defined medium or medium supplemented with 5% FBS or 5% HuS. In all cases examined, defined medium and medium containing HuS were superior to medium containing FBS in supporting growth of both normal and tumor cell cultures. However, cultures in defined medium showed an initial cell loss. Cells from the same tumor cultured in different media varied in their responses to chemotherapeutic agents. In light of these results, medium supplemented with HuS, which promoted attachment of these cells in culture and stimulated their growth, should be the most appropriate nutrient environment for determining the effects of therapeutic agents on cells as it most closely resembles the in vivo situation. Because there were also variations in growth rates and chemosensitivities of tumor cells cultured in different human serum samples, we suggest that optimal conditions in which to culture these cells include the serum of the patient whose tumor is removed. This serum may provide host factors that influence cell growth and interact with exogenous factors.

Topics: Animals; Antineoplastic Agents; Blood; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cattle; Cell Division; Cells, Cultured; Culture Media; DNA; Doxorubicin; Epithelium; Female; Fetal Blood; Fluorouracil; Humans; Melphalan; Microscopy, Electron

Osteonecrosis (aseptic or avascular necrosis of bone) is an entity with many causes that can occur at a variety of sites. It is a known complication of corticosteroid therapy, either alone or combined with other drugs in the treatment of malignancy. Osteonecrosis associated with chemotherapy that does not include corticosteroids is rare; three such cases have been reported in the English literature. One received cyclophosphamide alone, another vinblastine and bleomycin, while the third received cyclophosphamide, methotrexate, and 5-fluorouracil. The authors report a 40-year-old woman who had a left radical mastectomy in 1978 and a right radical mastectomy in 1980 for infiltrating ductal adenocarcinoma of the breasts. She received melphalan following the first surgery and a combination of doxorubicin, cyclophosphamide, and 5-fluorouracil after the second operation. In 1984 she noted pain in both knees that slowly increased in severity. A bone scan revealed increased periarticular activity in the medial and lateral femoral condyles of both knees compatible with bilateral osteonecrosis. There was no evidence of metastatic carcinoma on the bone scan. The patient was treated surgically with drilling and autologous bone grafting. A bone biopsy at the time of surgery revealed osteonecrosis but no metastatic adenocarcinoma.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cyclophosphamide; Doxorubicin; Female; Femur; Fluorouracil; Humans; Melphalan; Osteonecrosis; Radiography

The effect of known chemotherapeutic programs in patients with breast cancer who developed metastasis during or after adjuvant chemotherapy with L-PAM plus 5-FU (PF) were studied. Thirteen patients failed while receiving adjuvant therapy at 3-22 months from the time therapy started. Three patients failed 6-28 months after 2 years of therapy. Thirteen patients received PF followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) at the time of progression on PF. Of these, ten received Adriamycin and vincristine (AV) at the time of progression on CMF. The response to CMF was 7%. No patient responded to AV after progression on CMF. Two of three patients treated with AV after failure on PF did respond, but both for only 6 months. This suggests that adjuvant therapy may render the tumor less responsive to further chemotherapy. Since most patients failed while on adjuvant therapy, this may indicate a poor prognosis regardless of the agents used.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Melphalan; Methotrexate; Middle Aged; Neoplasm Metastasis; Prognosis; Tamoxifen; Vincristine

One hundred and thirty three specimens from mammary and ovarian adenocarcinoma and from melanoma were cultured according to an agar/agar clonogenic assay. Melanoma and ovarian cancers exhibited a 70 per cent rate of success for culture; 50 per cent of the mammary adenocarcinomas were successfully cultured. Fifty-nine ovarian cancers were cultured in order to test the in vitro effectiveness of Cisplatinum and Adriamycin. Thirty percent of cultured tumors gave rise to relevant chemograms. The chemoresistance measured in vitro was correlated to the ineffectiveness of the patient's treatment. In contrast, we were unable to predict chemosensitivity. Taking into account the technical difficulties encountered in these assays, human tumor clonogenic assays cannot at present be proposed as a routine procedure in the prediction of the effectiveness of chemotherapeutic treatments. Nevertheless, they must be developed in order to determine the spectrum of activity of new antineoplastic agents on various human tumors.

Topics: Adenocarcinoma; Agar; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cisplatin; Colony-Forming Units Assay; Cyclophosphamide; Doxorubicin; Drug Resistance; Female; Humans; Melanoma; Melphalan; Ovarian Neoplasms; Tumor Stem Cell Assay