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Biomedical subjects

F M Muggia

Publications and source records attributed to F M Muggia.

At least 145 records · Page 8Linked to original sources
PubMed1986

Cisplatin and vinblastine chemotherapy for metastatic non-small cell carcinoma followed by irradiation in patients with regional disease.

Forty-four patients with non-small cell carcinoma of the lung were treated every 3 weeks with vinblastine (4 mg/m2/day iv X 2) and cisplatin (20 mg/m2/day iv X 3). Of the 28 patients with metastatic disease, eight (29%; 90% confidence interval of true response, 17%-47%) achieved objective response, for a median duration of 27 weeks. Median survival in this group was 47 and 28 weeks for responders and nonresponders, respectively. Of the 16 patients with advanced regional disease, 11 (69%; 90% confidence interval of true response, 49%-86%) achieved objective response. Thirteen of these patients received consolidation radiotherapy (4500 cGy/25 fractions/5 weeks), with a boost of 1000 cGy/5 fractions/1 week in those patients who achieved response. In the three patients who did not receive radiotherapy, two died during the induction phase, one from grade 4 leukopenia and sepsis and the second from unrelated factors. The third patient had systemic progression of disease during induction chemotherapy. Six patients experienced overall improvement in their chemotherapy response from the radiotherapy. Two patients who did not respond to the chemotherapy achieved partial response with irradiation. Four patients who had partial response to the chemotherapy achieved complete response with irradiation, and seven patients had no further change in their degree of response to irradiation. The overall median survival of this group was 81 weeks. Maintenance chemotherapy was not given. After radiotherapy, the site of first failure was outside the radiation field in nine of 13 patients (69%). Hematologic toxicity was dose-limiting. Other toxic effects that were not dose-limiting included nephrotoxicity, neurotoxicity, and acute nausea and vomiting. In the patients with advanced regional disease, there was no increase in the radiation toxicity attributable to the chemotherapy. We conclude that: (a) this dose schedule of vinblastine and cisplatin has reproducible activity in non-small cell carcinoma of the lung; (b) the response and median survival of patients with advanced regional disease are superior to those of patients with metastatic disease; and (c) in patients with advanced regional disease, treatment with chemotherapy followed by radiotherapy yielded an overall response rate of 81% (90% confidence interval of true response, 60%-93%) and improved survival compared to a similar group of patients studied by others receiving radiotherapy alone. We recommend further testing of this concept.

Adult↗
PubMed1985

Phase II trial of PCNU in advanced malignant melanoma: an Eastern Cooperative Oncology Group pilot study.

PCNU, a chloroethylnitrosourea with high alkylating activity, low carbamoylating activity, optimal octanol: water partition coefficient and broad activity in animal systems, was administered to 32 evaluable patients with measurable metastatic melanoma by brief intravenous infusions every six weeks. The initial dose was 75 or 100 mg/m2, with escalation or reduction for toxicity, and a total of 58 evaluable courses were given. Half of the patient population had received no prior chemotherapy. One objective complete response (duration 585 days) and four objective partial responses (durations 55, 169, 405 and 102 days) occurred, the last recorded in a patient previously treated with DTIC. These responses included visceral, nodal and subcutaneous disease. The response rate was 16% with a 95% confidence interval of 5.5 to 33.7%. Thrombocytopenia was dose-limiting and leukopenia was relatively mild. Gastrointestinal toxicity was less severe than expected for a nitrosourea. PCNU has comparable clinical activity to that of other nitrosoureas in patients with advanced melanoma.

Adult↗
PubMed1985

Testicular cancer and the legacy of chemotherapy.

The treatment of testicular cancer has undergone considerable evolution since the introduction of cisplatin and the widespread recognition of its curative potential in all stages of disease. Chemotherapy developments that have taken place include substitution of etoposide for vinblastine in some primary combinations and high-dose cisplatin regimens for patients with otherwise poor prognosis. Definition of timed survival restaging and reassessment of the role of radiation has taken place. In early disease stages, dissection of retroperitoneal nodes combined with either a short course of adjuvant chemotherapy or careful monitoring followed by salvage chemotherapy has yielded impressive results (greater than 90% cures) in node positive patients. These results have encouraged trials including careful follow up for patients with negative retroperitoneal and other findings (markers, computerized tomography) on clinical staging alone. Evolution of these treatment strategies should take place within the context of prospectively designed studies. In this brief overview of developments, we point out how the legacy from the successful application of chemotherapy will form the basis for additional achievements which will include the introduction of second-generation drugs and optimization of combined modality strategies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Prospective evaluation of cardiotoxicity during a six-hour doxorubicin infusion regimen in women with adenocarcinoma of the breast.

In order to test the possible cardiac-sparing effect of doxorubicin administered by six-hour intravenous infusion and to prospectively evaluate the role of resting left ventricular ejection fraction in monitoring these patients, 33 women with advanced breast cancer were treated with combination chemotherapy containing 5-fluorouracil, cyclophosphamide, and doxorubicin. Doxorubicin was administered via a femoral catheter as a six-hour infusion. Cardiac function was monitored prior to therapy and at intervals during therapy by history and physical examination and by measurement of resting left ventricular ejection fraction with gated pool radionuclide angiography. Twenty-six responses were observed (complete response, seven [21 percent]; partial response, 19 [57 percent]). Systemic toxicity included alopecia, myelosuppression, and nausea and vomiting. There was a progressive fall in resting left ventricular ejection fraction during treatment from a median baseline value of 0.63. Mean fall from baseline left ventricular ejection fraction at a cumulative doxorubicin dose of 200 to 300 mg/m2 was 0.06 (p less than 0.005); at 301 to 449 mg/m2 it was 0.09 (p less than 0.0005); and at 450 mg/m2 or greater it was 0.15 (p less than 0.0005). Clinical congestive heart failure developed in three patients. Even though the decrease in left ventricular ejection fraction was often within the "normal range" (left ventricular ejection fraction 0.50 or greater), these changes were progressive and appeared to be part of a continuum of doxorubicin-induced myocardial damage. Steady-state infusion levels of doxorubicin in plasma ranged from 90 to 120 nM. They confirm the hypothesis that lower concentrations can be achieved by continuous infusion rather than by bolus infusion. In this study, however, administration of doxorubicin by six-hour infusion did not appear to have a major cardiac-sparing effect. Studies of anthracycline cardiac toxicity should include determination of baseline left ventricular ejection fraction and serial observations during therapy. Failure to include deteriorations in function above an arbitrary cutoff point or to make observations only at higher cumulative doses may underestimate drug-induced myocardial damage.

Adenocarcinoma↗
PubMed1985

A phase II study of bisantrene in advanced refractory breast cancer. An Eastern Cooperative Oncology Group pilot study.

Thirty patients with advanced refractory breast cancer received bisantrene 260 mg/m2 intravenously every 3 weeks. Reversible myelosuppression was the most commonly observed side effect. Four patients (13.3%) achieved objective partial response (90% confidence intervals 3-24%), while two patients (6.6%) had disease improvement with a PR + IMP rate of 19.9%. Seven additional patients (23.3%) had stabilization of disease. This drug has antitumor activity against breast cancer and warrants further study, particularly if problems with drug delivery are overcome.

Adult↗
PubMed1985

4'Epidoxorubicin (epirubicin): activity in hepatocellular carcinoma.

Doxorubicin provides the most consistent response rate in hepatocellular carcinoma. We therefore initiated a trial with its analog 4'epidoxorubicin. Eighteen patients, all without prior treatment, were given the drug as a single agent every 3 weeks with dose escalation whenever possible. Five patients were treated by six-hour infusion and 13 by intravenous (IV) bolus injection, with the median dose being 90 mg/m2. The patients were of diverse ethnic background and included some with underlying cirrhosis and hepatitis B surface antigenemia. Three patients had partial remissions (6, 12, 48 weeks) for a response rate of 17%. Four patients also had prolonged stable disease (14, 26, 27, 38 weeks). Toxicity was mild, although cardiac toxicity developed in three patients at 685, 825, and 1,460 mg/m2 cumulative dose. The response to 4'epidoxorubicin in this study appears to be equivalent to the reported response rates for doxorubicin, with decreased toxicity.

Adult↗
PubMed1985

Colorectal cancer: speculations on the role of intraperitoneal therapy.

Treatment of colorectal cancer beyond surgical resection has had only minimal success in the past. Studies are therefore examining the most advantageous use of currently available treatment methods. Most experience with colorectal cancer has involved 5-fluorouracil; alternatives for adjuvant therapy include combination therapy, immunotherapy, and locoregional therapy. Some success has also been reported with portal vein infusion or intraperitoneal administration of chemotherapeutic agents. Comparison of recurrence data indicates that approximately one third of patients with extrapelvic colorectal cancer can be expected to have peritoneal seeding. Many factors, including selection of patients and chemotherapeutic agents, method of administration, devices used, and techniques for monitoring patients affect the results of any clinical study. Future directions for the adjuvant treatment of colorectal cancer might involve the addition of other agents to the intraperitoneal regimen or of whole abdominal or liver radiation, and also concomitant systemic or portal vein 5-fluorouracil.

Antineoplastic Agents↗
PubMed1984

Role of chemotherapy in the treatment of lung cancer: evolving strategies for non-small cell histologies.

Lung cancer treatment has been considered to have made little progress except for advances in small cell carcinoma. For other histologies an attitude of nihilism has prevailed principally because of lack of effective systemic therapy and of no persuasive evidence that results could be improved by combined modality treatment. On the other hand, favorable results from surgery are confined to a small percent of all patients with this disease. This review emphasizes possibilities for progress in evolving new therapeutic strategies. Although improvement over other systemic therapies is modest, cisplatin-containing regimens yield more consistent response rates and apparent survival advantage relative to single agents. Immediate progression occurs in the minority of patients. In addition, regimens combining cisplatin with vinca alkaloids have no substantial deleterious effects on the lung, marrow or esophagus to aggravate radiation-induced complications. These features encourage the evolution of strategies which begin with chemotherapy and then use consolidation with radiation therapy. Clinical trials using these and newer strategies must be instituted if progress is to occur in the treatment of non-small cell histologies at all stages.

Adenocarcinoma↗