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Biomedical subjects

M Perloff

Publications and source records attributed to M Perloff.

At least 37 records · Page 2Linked to original sources

Hyperglycemic complications associated with adjuvant chemotherapy of breast cancer. A cancer and leukemia group B (CALGB) study.

Many adjuvant chemotherapy regimens used for breast cancer include prednisone, which has the potential to cause hyperglycemia. We reviewed the results of three CALGB studies employing prednisone as part of adjuvant therapy to determine the incidence and severity of hyperglycemic complications. All treatment regimens included cyclophosphamide, methotrexate or doxorubicin, 5-fluorouracil, and vincristine in addition to prednisone. Among 1,237 evaluable patients receiving a five-drug regimen including prednisone, there were 98 patients (7.9%) who experienced any degree of hyperglycemia. Thirty patients (2.4% overall; 30.6% of those having any hyperglycemia) had severe or life-threatening degrees of hyperglycemia, including two patients whose hyperglycemia contributed directly to death. We conclude that prednisone administration as part of adjuvant chemotherapy regimens in breast cancer produces an appreciable incidence of hyperglycemia. Serum glucose levels should be monitored during therapy to help prevent the occasional severe or life-threatening episode of hyperglycemia in these patients.

Antineoplastic Combined Chemotherapy Protocols↗

Adjuvant therapy for breast cancer patients with negative lymph nodes.

Although approximately 50,000 cases of axillary node-negative breast cancer are diagnosed in the United States annually, the natural history of this heterogeneous disease is incompletely defined. Several series have reported 5-year relapse-free and overall survival ranging from 56% to 89% and 74% to 92%, respectively. Tumor necrosis and anaplastic morphology correlate with early treatment failure. The estrogen receptor and size of the primary tumor are probably also predictive of clinical course. Thus far, perioperative cyclophosphamide is the only systemic treatment demonstrated to prolong survival in a statistically significant fashion. Several ongoing studies are investigating the role of tamoxifen or cytotoxic chemotherapy, or both, in prospective randomized trials. However, too few patients with insufficient follow-up have been analyzed to permit definitive conclusions or recommendations.

Antineoplastic Agents↗

A comparison of intermittent vs. continuous and of adriamycin vs. methotrexate 5-drug chemotherapy for advanced breast cancer. A Cancer and Leukemia Group B study.

The therapeutic effectiveness of intermittent vs. continuous combination chemotherapy and of the substitution of adriamycin for methotrexate in a 5-drug regimen was evaluated in women with metastatic breast carcinoma. Patients were randomly allocated to receive continuous therapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone ( CMFVP -C, 86 patients), intermittent CMFVP ( CMFVP -I, 109 patients), or intermittent CAFVP (107 patients). The CR + PR rate with CAFVP (71%) was superior to CMFVP -C (50%, p = 0.003) and to CMFVP -I (50%, p = 0.002). The remission duration with CAFVP (14 months, median) was superior to CMFVP -I (7 months) (p less than 0.01), and tended to be superior to CMFVP -C (9 months) (p = 0.07). There was a survival advantage of CAFVP (19 months, median) over CMFVP -I (13 months) (p = 0.01), but not over CMFVP -C (16 months) (p = 0.24). Among CR + PR patients, the survival with CAFVP (29 months, median) was superior (p = 0.02) to both CMFVP -I (18 months) and CMFVP -C (21 months). The CMFVP -C regimen was associated with the highest incidence of leukopenia and neurologic toxicity, but the lowest incidence of GI toxicity. The results indicate that the CAFVP regimen is well tolerated and is superior to the CMFVP regimens.

Age Factors↗

A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer.

Women with breast carcinoma and four or more involved ipsilateral axillary lymph nodes were randomly assigned to receive an induction course and 2 yr of maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF, 150 patients), CMF plus vincristine and prednisone (CMFVP, 166 patients), or chemoimmunotherapy with CMF plus the methanol extraction residue of BCG (CMF-MER, 85 patients). After 5 yr of accrual and a median follow-up of 34 mo, CMFVP is superior to CMF (p less than 0.01) with disease-free survival estimates at 4 yr of 60% for CMFVP compared to 45% for CMF. The disease-free survival advantage of CMFVP over CMF was greater in postmenopausal (p = 0.02) than in premenopausal patients (p = 0.09). CMF-MER was similar to CMF alone. CMF related side effects were similar in each regimen (see text), except for a greater incidence of leukopenia during induction with CMF than with CMFVP (p less than 0.01).

Adult↗

Chemotherapy before and after mastectomy in stage III breast cancer.

Seventeen patients with stage III breast cancer were treated by modified radical mastectomy preceded and followed by multiagent cytotoxic chemotherapy. The preoperative treatment resulted in a decrease in size of the primary tumor, facilitating the subsequent surgical procedure. There were no serious surgical complications. Wound healing was uneventful. Median disease-free survival time was 29 months and median survival time was 40+ months. Six of the 17 patients are living free of recurrence from more than 33 to more than 79 months after initial therapy.

Adult↗

A randomized trial of postoperative five-versus three-drug chemotherapy after mastectomy: a Cancer and Leukemia Group B (CALGB) study.

The Cancer and Leukemia Group B (CALB) has conducted a randomized study of adjuvant chemotherapy in patients with breast cancer who have involved axillary nodes at the time of mastectomy. Five-drug treatment (CMFVP) was compared with three-drug treatment (CMF). For patients with more than three involved nodes, the CMFVP regimen produced a significantly prolonged disease-free survival in comparison to the CMF regimen.

Breast Neoplasms↗

One-day VATH (vinblastine, Adriamycin, thiotepa, and Halotestin) therapy for advanced breast cancer refractory to chemotherapy.

Twenty-nine postmenopausal patients with metastatic breast cancer refractory to conventional combination chemotherapy underwent treatment with a combination of vinblastine, Adriamycin, thiotepa, and Halotestin given once every 21 days. Thirteen patients (45%) responded with a greater than 50% regression of measurable tumor. Responses occurred in nine of 12 patients (75%) with visceral dominant disease and were recognized in four of 15 (27%) with osseous dominant disease (another 5 improved for a total improvement of 60%). The median duration of response was 11 months. The median survival times were 16 months for responders and eight months for those with progressive disease. Response rate was not affected by age, number of years after menopause, number of metastatic sites involved, or number of systemic treatment modalities previously used, but may have been adversely affected by late stage at original diagnosis, short time from diagnosis, poor response to primary chemotherapy, and dose modification. This combination of drugs is a convenient, tolerable, and effective regimen for treating breast cancer refractory to primary chemotherapy regimens currently in use.

Adult↗

Cystosarcoma phylloides: a case presentation.

A case of cystosarcoma phylloides is presented here showing the natural history of this disease both clinically and pathologically from 1962 through 1979, and demonstrating the management of this disease by surgery and by chemotherapy with the use of adriamycin at 25 mg/m2 daily, times three days, every 28 days, which to out knowledge has not been used in this particular setting.

Breast Neoplasms↗

Radioisotopic 51Cr-leukocyte adherence inhibition (LAI) assay. I. Demonstration of anti-tumor immunity in patients with breast carcinoma.

A simplified radioisotopic leukocyte adherence inhibition assay (51Cr-LAI assay) was used to determine tumor-directed immune responses in patients with cancer of the breast. Essential steps in development of this assay are the standardization of conditions for optimal 51Cr uptake by peripheral blood lymphocytes (PBL) and the inclusion of autologous or normal AB serum in the incubation media. A dextrose salt mixture (GNK) was found to enhance intracellular uptake of 51Cr significantly (8-fold) without affecting viability of the cells or without causing selective loss of lymphocyte subpopulations. The presence of 10% autologous or normal AB serum prevented non-specific LAI responses to unrelated tumor antigens. In a study of 46 preoperative patients with suspected breast cancer, clear and accurate prediction of the presence of cancer was achieved with this new assay. All patients with localized breast cancer showed significant adherence inhibition in response to allogeneic breast tumor extracts whereas normal control women and patients with benign diseases did not respond. Neither patients with cancer nor those with benign breast diseases reacted to extracts of benign breast tissue antigens. LAI reactivities appeared to be directed selectively against tumor-associated antigens (TAA) and reflect specific antitumor immunity. This short term (4 h) 51Cr-LAI assay provides reproducible and specific results analogous to those using tube-LAI assay. The test has the advantages of being accurate, sensitive and free from technical bias.

Adult↗

High dose methotrexate followed by citrovorum factor reversal in patients with advanced cancer.

High dose methotrexate followed by citrovorum factor reversal has been utilized in twenty-six patients with advanced cancer. Four of 10 patients with head and neck cancer had an objective response. One of 7 patients with metastatic osteosarcoma to the lungs had stabilization with twenty treatments over 23 months. One patient with acute lymphocytic leukemia developed marrow aplasia but did not attain remission. The regimen was well tolerated when meticulous attention was paid to hydration, urine alkalinization, renal function and third space fluid accumulation. Life-threatening or lethal toxicity was encountered when these phenomena were not scrupulously observed.

Adolescent↗

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

Nineteen postmenopausal patients with metastatic breast cancer refractory to conventional combination chemotherapy were treated with monthly cycles with the combinations 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.

Adult↗

Hepatocellular carcinoma in a young woman with prolonged exposure to oral contraceptives.

A case of hepatocellular carcinoma in a young female is presented in which the apparent etiology was the use of oral contraceptives for 5 1/2 years. Sequential therapeutic trials with intraarterial 5-fluorouracil, intraarterial adriamycin, and intravenous 1,3 bis[2-chloroethyl]-1-nitrosourea (BCNU) were unsuccesful. The adverse effects of oral contraceptives on the structure and function of hepatic tissue are reviewed.

Adult↗

Surgical adjuvant chemotherapy.

The evidence that the principles of surgical adjuvant chemotherapy developed in experimental animal systems also apply to a variety of neoplastic diseases in man has been clearly demonstrated. Micrometastatic disease can be eradicated with effective chemotherapy in several diseases. Prolongation of disease-free interval, if not cure, is now possible in diseases in which curative surgery alone or in combination with radiotherapy does not achieve these goals. The previously fatal childhood solid tumors--Wilms', Ewings' sarcoma, embryonal rhabdomyosarcoma--are curable in a high percentage of patients appropriately treated with combinations of surgery, radiotherapy, and chemotherapy. The prolongation of the disease-free interval in osteogenic sarcoma has permitted consideration of entirely new surgical approaches for this tumor in which radical amputation has traditionally been employed. The spectacular results achieved in the treatment of Stage II breast cancer may potentially save hundreds of thousands of lives in the coming decade. Clinically recognizable metastatic disease is rarely curable by any currently available treatment modality. The prolongation of disease-free intervals and production of cures when surgical adjuvant chemotherapy is employed may be partly explained by relatively more circulation, and thus drug delivery to each tumor cell, more favorable cellular kinetics, and a healthier and more immunocompetent host who is better able to withstand drug effects on normal tissues, and to participate in tumor destruction. Cures of certain patients with neoplastic diseases using surgical adjuvant chemotherapy has increased the incentive to learn more about new and old drugs and their effective use alone and in combination. Chemotherapy, in appropriate combinations with surgery, radiotherapy, and immunotherapy, may well be more efficacious in many clinical situations than the traditional use of single-modality treatment. The data presented in this paper relate solid evidence that the possibility of cure in a variety of neoplastic diseases is real.

Adult↗

Effects of methanol extraction residue of Bacillus calmette-Guérin in humans.

Forty patients with histologically confirmed neoplastic diseases were treated with the methanol extraction residue of Bacillus Calmette-Guérin (MER). Thirty-six received concomitant chemotherapy. MER was initially given intradermally twice a month, 1 week apart, at a dose of 200 mug into each of five sites draining different lymph node-bearing areas on the anterior body surface. Thirty-seven patients developed local ulcerations at least 0.5 cm in diameter at MER injection sites. Typical lesion evolution was characterized by erythema and induration followed by vesicle formation and central necrosis. Either granulation tissue or a thick nonulcerated eschar preceded healing, leaving a linear, flat scar. Systemic toxicity consisted of malaise, fever, and myalgias on the day of MER administration. No hematological or biochemical changes directly attributable to MER were observed. Dose titrations in decreasing 10-fold dilutions in a linear array in a single anatomical region were carried out on 35 occasions. All patients but three developed at least a 5-mm induration to the 1-mug dose within 2 weeks of titration. Dose reductions were necessary in 19 instances. The minimal dose that produced a 1-cm inflammatory lesion with central necrosis was 0.01 mug. Serial biopsies were performed. These indicated a time-related series of changes from a nonspecific inflammatory lesion to an acute inflammatory response with microabscesses, followed by noncaseating granulomata and ultimately fibrosis. MER is a quantifiable nonviable immunostimulant that obeys dose-response relationships in its cutaneous lesions.

Antineoplastic Agents↗

Combination chemotherapy with adriamycin and cis-diamminedichloroplatinum in patients with neoplastic diseases.

Forty-eight patients with a variety of advanced solid tumors were treated with a combination of adriamycin 50 mg/m2, and cis-diamminedichloroplatinum 50 mg/m2, every 2 to 4 weeks. Fifteen patients responded with a greater than 50% regression of measurable tumor; six with lung cancer; one, carcinoma of the breast; one, ovary; one, cervix; one, prostate; one, testis; one, maxillary sinus; and one, salivary gland, plus one patient with chemodectoma and one with adenocarcinoma of unknown primary. Responses lasted 1 to 18 months, with a median of 6 months. An additional six patients, including two with adenocarcinoma of the lung three with carcinoma of the cervix, and one with embryonal cell testicular carcinoma improved (25-50% regression of the tumor). Toxicity encountered included myelosuppression, azotemia, alopecia, nausea, vomitting, and stomatitis. Severe hematologic toxicity occurred only in those with compromised marrow function or with concurrent active hepatitis. Major potentiation of toxicity by the combination does not appear to have occurred.

Adolescent↗

Combination amphotericin B-rifampin therapy for pulmonary aspergillosis in a leukemic patient.

Pulmonary aspergillosis developed in a 62-year-old man with acute myelogenous leukemia. Therapy with amphotericin B and 5-fluorocytosine was begun. Synergy between amphotericin B and rifampin was demonstrated in vitro, and therapy with firampin replaced 5-fluorocytosine. Progressive clearing of the pulmonary lesion ensued, suggesting in vivo efficacy as well. Further studies of patients utilizing this regimen are warranted.

Amphotericin B↗