Searched for: person:muggif01
Noninvasive monitoring of drug biodistribution and metabolism: studies with intraarterial Pt-195m-cisplatin in humans
Shani, J; Bertram, J; Russell, C; Dahalan, R; Chen, D C; Parti, R; Ahmadi, J; Kempf, R A; Kawada, T K; Muggia, F M
We have performed a comparative evaluation of systemic (i.v.) and intraarterial (i.a.) cisplatin by using a trace dose of the radiolabeled form of this drug [( 195mPt]cisplatin) to monitor the drug's biodistribution by dynamic scintigraphic imaging. We have analyzed the drug's metabolism using a compartmental model both following i.a. and i.v. administration in patients with gliomas. Significantly larger amounts of radioactivity (up to 10 times higher than in the uninvolved brain) were measured in tumors following i.a. administration, whereas the differential localization following i.v. drug administration was, at best, only twofold that of the uninvolved brain. On the other hand, no significant differences could be detected in the pharmacokinetics of either free cisplatin or platinated proteins in blood. The washout slope in tumors following i.a. administration may be an indicator of the higher local concentration of free cisplatin; no such washout could be observed in tumors following i.v. administration. The present noninvasive methods may help document the amount and the rate of (active) drug deposition at the desired target site. They may also assist in monitoring, prospectively and/or, on line, the probable effect of chemotherapy in an individual patient. In turn it may lead to novel methods for optimizing chemotherapeutic effectiveness at specific tumor-bearing sites and in defined treatment protocols.
PMID: 2924326
ISSN: 0008-5472
CID: 161368
Overview of carboplatin: replacing, complementing, and extending the therapeutic horizons of cisplatin
Muggia, F M
Carboplatin is the one platinum analogue that has received widespread clinical testing both in cancers that are normally targets for cisplatin and in others. It was introduced in 1981 because of its lesser toxicity and equivalent biochemical selectivity and antitumor spectrum relative to cisplatin in preclinical systems. Clinical studies have generally confirmed these expectations and given rise to interesting prospects in current cancer therapeutics. Carboplatin is as effective as cisplatin in ovarian cancer and considerably less toxic. Replacement of cisplatin by carboplatin seems likely in a number of other diseases where cisplatin has played a major role, especially if ongoing phase III studies confirm the regimens are equivalent. Carboplatin may also complement cisplatin's role by its innovative integration into treatment strategies, and by use of it as additional treatment when cisplatin's nonhematologic toxicities are prohibitive. Finally, although it is not likely to possess a different therapeutic spectrum than cisplatin, carboplatin appears to be extending the indications for platinum compounds to new areas such as acute leukemia, endometrial cancer, and breast cancer. In the latter, use of autologous bone marrow reconstitution permits the dose intensity needed for promising therapeutic results. Carboplatin has become the experimental platinum analogue of choice in a wide range of new clinical situations and in combinations with other modalities.
PMID: 2655099
ISSN: 0093-7754
CID: 161369
Phase I/II trial of thymostimulin in opportunistic infections of the acquired immune deficiency syndrome
Chachoua A; Green MD; Valentine F; Muggia FM
Fifteen patients with acquired immune deficiency syndrome (AIDS) and opportunistic infection, were randomized to receive treatment with either thymostimulin (TP-1) at 1 mg/kg for 14 days then weekly for 12 weeks or placebo. The objectives of this study were to evaluate the toxicity of TP-1 in this patient population and to make observations on clinical response as measured by time to second opportunistic infection (OI) and changes in laboratory parameters of immune function. The study demonstrates that TP-1 can be administered safely. There were no differences, however, in time to second OI or overall survival between patient groups. In addition, no change in the immune function could be detected in patients receiving thymostimulin
PMID: 2790539
ISSN: 0735-7907
CID: 10760
Cancer chemotherapy : concepts, clinical investigations, and therapeutic advances
Muggia, Franco M
Boston MA : Kluwer, 1989
Extent: xii, 238 p. ; 21cm
ISBN: 0898383811
CID: 2134
Progressive paresthesias after cessation of therapy with very high-dose cisplatin
Grunberg, S M; Sonka, S; Stevenson, L L; Muggia, F M
Control of cisplatin-induced nephrotoxicity and nausea/vomiting has enabled the development of very high-dose cisplatin regimens (monthly total dose, 200 mg/m2). Neurotoxicity is now recognized to be the dose-limiting toxicity of these regimens. However, during a pilot study involving 5 mg/m2 vinblastine and 100 mg/m2 cisplatin given every 28 days on days 1 and 8 for the treatment of advanced non-small-cell lung cancer, we noted a high incidence of progressive peripheral neuropathy, which continued for several months after the discontinuation of cisplatin chemotherapy. Of the six patients treated, four received at least three cycles of therapy (median total cisplatin dose, 685 mg/m2; range, 500-725 mg/m2). All four patients developed a progressive peripheral neuropathy, with a worsening of toxicity by 1-3 grades over the 2-3 months after cisplatin discontinuation. One patient progressed from grade I (mild paresthesia) to grade IV (inability to ambulate) over a period of 3 months after the discontinuation of therapy. Stricter rules for early dose de-escalation and discontinuation may be required for very high-dose cisplatin regimens. Delayed progressive neuropathy should be recognized as a possible late complication of this form of therapy.
PMID: 2556219
ISSN: 0344-5704
CID: 161370
Radiotherapy in the treatment of ovarian dysgerminoma [Letter]
Muggia, F M
PMID: 3182318
ISSN: 0360-3016
CID: 161371
Treatment of epidemic Kaposi's sarcoma with a combination of interferon-alpha 2b and etoposide
Krigel RL; Slywotzky CM; Lonberg M; Green MD; Andes WA; Kempf R; Gupta S; Grace W; Spiegel RJ; Muggia FM; et al.
A prospective clinical trial of concomitant interferon-alpha 2b and etoposide was conducted in 24 previously untreated patients with epidemic Kaposi's sarcoma. Eight of 21 evaluable patients (38%) achieved either a complete response (1 patient) or a partial response (7 patients). None of the responders had a prior history of opportunistic infection. Hematologic toxicity was severe, and 8 patients developed an opportunistic infection. The combination of interferon-alpha 2b and etoposide has modest activity, but no additive or synergistic activity was evident in the dose and schedule utilized in this study. The exact role for interferon-alpha in epidemic Kaposi's sarcoma, both as a single agent and in combinations, remains to be determined
PMID: 3049944
ISSN: 0732-6580
CID: 34859
Toxicity comparisons between two chemotherapy regimens as adjuvant or salvage treatment in nonseminomatous testicular cancer
Weiss, R B; Stablein, D M; Muggia, F M; Einhorn, L H; Golbey, R B; DeWys, W D
The Testicular Cancer Intergroup Study was initiated to evaluate the efficacy of adjuvant chemotherapy in Stage II and salvage therapy in Stage I nonseminomatous testicular carcinoma. Chemotherapy regimens of cisplatin, vinblastine, and bleomycin (PVB) or the same drugs plus cyclophosphamide and dactinomycin (VAB) were used at institution or cooperative group preference. A comparison of the toxicities of these two regimens shows that VAB caused significantly more mucosal, dermatologic, and otologic toxicity than PVB, and PVB caused more leucopenia. Both regimens were equally effective in controlling cancer. Either regimen could be used as chemotherapy in testicular cancer, and the decision about which one to use could be based on their differences in toxicity and degree of patient convenience.
PMID: 2454718
ISSN: 0008-543x
CID: 161373
A new look at radionuclides therapy in metastatic disease of bone (review and prospects)
Kim, S I; Chen, D C; Muggia, F M
Bone-seeking radionuclides have been used to treat bone pain due to metastatic bone disease for over 40 years. More than 10 clinical studies using radiostrontium (Sr-89) have shown benefit in about 70-80% of patients having refractory bone pain from prostate, breast and other metastatic bone cancers, with minimal hematological toxicity. Other radionuclides, such as, radiophosphate (P-32), Yttrium-90, lodine-131, Rhenium-186, have also been used. Tumor necrosis has been found within the range of beta irradiation from the surrounding shell of bone incorporating the radionuclide. New strategies using radionuclides may be able to provide more effective methods of treatment, perhaps, beyond palliation. For example, the effect of low dose continuous radiation can be potentiated by hypoxic cell sensitizers. In addition, the kinetics of radionuclide uptake and retention can be modulated to increase the dose of radiation delivered to osteoblastic metastatic lesions, such as osteosarcoma.
PMID: 2460020
ISSN: 0250-7005
CID: 161372
Phase I trial of escalating dose doxorubicin administered concurrently with alpha 2-interferon
Green MD; Speyer JL; Hochster HS; Liebes LF; Dunleavy S; Widman T; Wernz JC; Blum RH; Spiegel RJ; Muggia FM
The clinical use of alpha 2-interferon and doxorubicin is based on in vitro and preclinical in vivo observations of synergistic antitumor efficacy. To test this combination a Phase I clinical and pharmacokinetic study of the concurrent use of alpha 2-interferon and doxorubicin was initiated in patients with malignant solid tumors. Each 5-wk treatment cycle consisted of 3 wk of drug administration and 2 wk of rest. The alpha 2-interferon was administered s.c. at a constant dose of 10 million IU/m2 on Mondays, Wednesdays, and Fridays in all patients while the doxorubicin was administered weekly beginning with a dose of 5 mg/m2 and escalated to the maximum tolerated dose of 25 mg/m2. At least three evaluable patients were entered at each dose level, and no dose escalations were allowed within patients. The dose-limiting toxicities were granulocytopenia and thrombocytopenia. Hepatic enzyme elevations and systemic symptoms due to interferon occurred at all dose levels. None was severe or dose limiting, and all were reversible. These toxicity data suggest that the hepatotoxic effects of interferon do not enhance doxorubicin toxicity when given by this dose and schedule. Doxorubicin plasma levels were measured at each dose level. The recommended dose of doxorubicin is 25 mg/m2 per wk when administered with 10 million IU/m2 of interferon in this schedule. This schedule allows for the administration of a greater total dose of doxorubicin than has been achieved when given every 3 wk with the same dose and schedule of alpha 2-interferon in a parallel study
PMID: 3356017
ISSN: 0008-5472
CID: 11108