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Biomedical subjects

F M Muggia

Publications and source records attributed to F M Muggia.

At least 163 records · Page 9Linked to original sources

Multidisciplinary considerations in cancer treatment: origin and scope.

The Tumor Board constitutes the control area where multidisciplinary protocols are created and where each patient's circumstance is thoroughly reviewed from the perspective of all pertinent clinical disciplines. Such input is an essential component of quality control at all levels of management of the cancer patient. This pertains whether in a community hospital or in a specialized cancer center. Cooperative groups and other research organizations have recognized the essential nature of this input, especially for the integration of new measures with those therapeutic modalities that are already established. Thus treatment may show a logical evolution by continuously updating standard approaches through clinical trials posing the most relevant question from the point of view of all modalities, while maintaining stringent quality control. Examples of questions being posed by therapeutic advances in testicular and ovarian cancer are described. The key element in accomplishing these advances is multidisciplinary participation.

Combined Modality Therapy↗

Phase II trial of cyclophosphamide and cis-platinum for non-small cell bronchogenic carcinoma.

We hypothesized that cyclophosphamide and cis-platinum, without adriamycin, which had been used in previous studies, may be equally efficacious, but less toxic. We treated 27 patients with non-small cell bronchogenic carcinoma with the combination of cyclophosphamide and cis-platinum. We report six responses (25% response rate), with median survival of 79 weeks as compared to 28 weeks in nonresponders (p less than 0.01). Our regimen had acceptable hematologic toxicity and tolerable gastrointestinal toxicity. However, cumulative nephrotoxicity and neurotoxicity were observed. We conclude that cyclophosphamide and cis-platinum may compare favorably to the cyclophosphamide, adriamycin and cis-platinum combination, with respect to response and toxicity.

Adult↗

Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine.

An epidemic of disseminated Kaposi's sarcoma in male homosexuals has recently been described. Forty-one evaluable patients with epidemic Kaposi's sarcoma were treated with etoposide. The majority of these patients had early stage disease, no prior opportunistic infections, and no prior therapy. Twelve patients (30%) achieved complete remission, 19 (46%) partial remission, and ten (24%) no response. With follow-up time to 31 months, the median response duration is nine months. The median survival of patients with complete and partial remissions has not been reached. A combination of doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), bleomycin, and vinblastine (ABV) was used in 31 evaluable patients with epidemic Kaposi's sarcoma. The majority of these patients had late stage disease, prior opportunistic infections, or had failed prior treatment. Seven patients (23%) achieved complete remission, 19 (61%) partial remission, and five (61%) no response. With follow-up time to 24 months, the median response duration is eight months. The projected median survival for all patients treated with ABV is nine months. Both regimens were well tolerated, with an overall response rate of 76% for etoposide and 84% for ABV. However, while successfully treating the Kaposi's sarcoma, the underlying immune deficiency in these patients has persisted. Future treatments of Kaposi's sarcoma will need to focus on reversing the underlying immune incompetence as well as controlling the malignant manifestations of Kaposi's sarcoma arising in relation to the acquired immune deficiency syndrome.

Adult↗

Phase II trial of PALA in lymphoma: an Eastern Cooperative Oncology Group study.

A phase II trial of PALA in malignant lymphoma was carried out by the Eastern Cooperative Oncology Group. The occurrence of hematologic toxicity in 17 of 35 patients in the study was noteworthy and was possibly related to prior therapy and/or marrow involvement. The finding of thromboembolic phenomena in four of five autopsied patients was also noteworthy. No antitumor activity was recorded. This experience discourages further trials of PALA in patients with malignant lymphoma.

Adult↗

Evaluation of a sequential 5-FU and hydroxyurea combination in advanced bowel cancer.

Twenty-nine patients (two with small bowel cancer and 27 with colorectal cancer) were treated with a sequential 5-FU-hydroxyurea combination following the suggestion of schedule-dependent synergism in experimental systems. No enhanced toxicity was observed, but the response rate was only 4%. Seven additional patients manifested greater than or equal to 50% declines in CEA, but caution must be used in interpreting such changes as antitumor activity.

Adult↗

Activity of mitolactol in cancer of the uterine cervix.

Antitumor activity has been documented in this pilot study utilizing mitolactol in patients with advanced carcinoma of the cervix. These results may in part be explained by optimal patient selection; however, the results do encourage further testing of this hexitol in this disease.

Adult↗

Repeated femoral vein cannulation for administration of chemotherapeutic agents.

A cannulation set has been designed for repeated short-term infusion of vesicant chemotherapeutic agents via the femoral vein. The major complication was thrombophlebitis in 2.1% of infusions. The procedure provides reliable venous access when therapeutic plans are changed or when the inability to provide catheter care makes an indwelling catheter unwarranted.

Antineoplastic Agents↗

Kaposi's sarcoma: a new staging classification.

Reports of an unusual form of Kaposi's sarcoma in young homosexual men in North America have demonstrated that previous classification systems for this disease are incomplete. We describe the clinical characteristics of 49 homosexual men with Kaposi's sarcoma and propose a new staging for the disease. There appear to be four clinically distinct forms of Kaposi's sarcoma: stage I--the more typical locally indolent lesions occurring predominantly in elderly males in North America and Europe; stage II--a locally invasive and aggressive form seen almost exclusively in equatorial Africa; stage III--a disseminated mucocutaneous form, often with lymph node involvement, seen primarily in African children and North American male homosexuals; and stage IV--a disseminated, mucocutaneous form with visceral involvement also seen in African children and North American male homosexuals. These stages are further subtyped as to the presence or absence of the systemic signs of unexplained fever and/or weight loss. Further longitudinal follow-up of these recently diagnosed cases will hopefully document that this proposed staging system correlates with survival data and is useful in the evaluation of treatment regimens for uniformly defined patient groups.

Adult↗

Phase I clinical trial of 9,10-anthracene dicarboxaldehyde (Bisantrene) administered in a five-day schedule.

Bisantrene is a substituted anthracene derivative which preclinically demonstrated a spectrum of activity similar to that of doxorubicin but without associated cardiotoxicity. A Phase I evaluation of the drug has been performed using daily i.v. administrations for 5 days. Sixty courses of treatment were administered to 23 patients at doses from 2.5 to 90 mg/sq m/day. Courses were repeated at 4-week intervals. Dose-limiting toxicities were leukopenia and local cutaneous reactions. The leukopenia was dose related, noncumulative, and of brief duration. Local reactions occurred in 14 of 37 courses administered at doses greater than 60 mg/sq m and in 13 patients resulted in clinical cellulitis of the infused extremity. Gastrointestinal side effects were mild. No alopecia or cardiotoxicity was observed. Two mixed responses were obtained in patients with hypernephromas. Using a daily schedule for 5 days, approximately 40% more drug can be delivered per course than by single-day i.v. administration. However, with this schedule, local cutaneous reactions may prove additionally dose limiting. Phase II studies of Bisantrene in a daily i.v. schedule for 5 days are planned at a dose of 80 mg/sq m/day to be repeated every 4 weeks.

Anthracenes↗

Clinical trials with the hexitol derivatives in the U.S.

Three hexitol derivatives, dibromomannitol (DBM), dibromodulcitol (DBD), and dianhydrogalactitol (DAG), originally investigated in Hungary, have been evaluated as anticancer agents in the United States. Their principal mechanism of action is attributed to alkylation via actual or derived epoxide groups. Their preclinical spectrum includes activity against murine leukemias and against the murine ependymoblastoma, which is particularly noteworthy for DAG. Dibromomannitol trials were targeted to chronic myelogenous leukemia but no advantage over busulfan therapy was demonstrable. Dibromodulcitol and DAG were sequentially evaluated for their usefulness against a wide variety of tumors. The activity of DBD against breast cancer has stimulated several continuing trials in this disease. On the other hand, DAG was disappointing in breast cancer and in several other malignancies, but some activity has been noted against lung cancer. Both DBD and DAG are being investigated for possible usefulness in the management of patients with intracranial neoplasms. The present clinical experience does not allow firm judgment on the advantage of one analogue over another. Such comparative analysis does point out the desirable direction of future studies as well as the limitations of current preclinical systems for the selection of analogues.

Animals↗