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F M Muggia

Publications and source records attributed to F M Muggia.

At least 181 records · Page 10Linked to original sources
PubMed1981

Selected anticancer drugs in Phase I trials in the United States (1979--1980).

Phase I trials in 1979 include some drugs representing totally new structures, new schedules of old compounds undergoing reevaluation, and second generation compounds. The rational development of analogs based on structure-activity relationships and on overcoming pharmacologic or toxicologic problems of parent compounds requires much future emphasis; two such examples (pentamethylmelamine and AZQ) are cited here. For all drugs, a plan of clinical development should ensure a more thorough initial evaluation as well as validation of concepts and systems that have prompted their introduction into the clinic. Establishment of clinical usefulness for the new structures, and particularly for three compounds herein reintroduced after a long period of oblivion, would constitute tangible proof of methodological and technological advances that have taken place in the development and clinical evaluation of anticancer drugs.

Animals↗
PubMed1981

Animal toxicology for early clinical trials with anticancer agents.

This analysis was carried out to assess quantitative and qualitative relationships between animal and human toxicology data with anticancer drugs. Among 21 chemotherapeutic agents, one-sixth LD10 in the mouse or one-third toxic dose low (TDL) in the dog corresponded to acceptable doses in man when experimental and clinical data were obtained at identical schedules and compared on a mg/m2 basis. The mouse and the dog largely differed in their tolerance to individual drugs. One-tenth LD10 in the mouse seemed always tolerated in the dog. On the average, these species were equally relevant for establishing the initial dose in man. A similar number of dose escalation steps would have been required in phase I clinical trials if the starting dose had been based on one-tenth LD10 in the mouse or the lowest value of one-sixth LD10 in the mouse and one-third TDL in the dog. These observations indicate that the starting dose in phase I clinical trials could be safely and efficiently based on one-tenth LD10 in the mouse. Prior verification that the resulting dose is not lethal or life-threatening in the dog could add further safety to this procedure. The predictive value (PV+) in man of organ system toxicity in animals depends upon the prevalence of this toxicity in man. In our study, PV+ was high (greater than 0.85) for common toxic effects in man, i.e., gastrointestinal intolerance and myelosuppression. PV+ declined dramatically (0.05 to 0.54) with rarer toxic manifestations. There was no clear superiority of animal findings over the mere knowledge of the prevalence of these findings in man. Thus, it would appear that routine and undiscerned investigation of organ system toxicity in animals is of questionable usefulness for the clinician experienced in early clinical trials with chemotherapeutic agents.

Animals↗
PubMed1981

Future clinical investigations with anthracycline antibiotics in relation to daunorubicin.

Future studies with daunorubicin involve mainly comparative evaluations with other anthracycline antibiotics and related compounds. Efforts are ongoing to improve the therapeutic index of these drugs. This includes not only laboratory development but also clinical evaluation of analogs, manipulations in dose schedules, and the use of protectors of toxic manifestations, primarily of cardiomyopathy. Technological advances in the clinical area permit, for example, the exploration of daunorubicin and related compounds by continuous infusion under more precise pharmacologic and cardiologic monitoring than was possible when they were initially introduced.

Aclarubicin↗
PubMed1981

Cisplatin: impact of a new anticancer agent on current therapeutic strategies.

This brief overview illustrates the role of cisplatin in current cancer chemotherapy. This new agent is increasingly utilized in first line regimens for a variety of tumor types notably testicular, head and neck and bladder cancer. Large scale investigations are taking place to evaluate these regimens in combined modality approaches to early stages of these diseases.

Antineoplastic Agents↗
PubMed1981

Clinical trials with diglycoaldehyde (NSC-118994): review and reasons for withdrawal from clinical trial.

All Phase II studies with diglycoaldehyde with leukemia and solid tumors have been reviewed. The dose schedules employed ranged from 1.5 to 2.0 g/m2/day for 3 to 5 days. The most common side effects have been gastrointestinal (nausea and vomiting), which occurred in 22% of the patients. Renal toxicity (rise in BUN, creatinine, and urinary proteins) was seem in 17% of the patients treated. Other infrequent toxicities include hypocalcemia (9%) and local complications such as phlebitis. Leukopenia, thrombocytopenia, positive Coombs' test and impairment in coagulation profile were also reported. In contrast to the hints of therapeutic efficacy described during Phase I trials, in phase II trials no activity was noted among 96 patients with solid tumors and only minimal antileukemic action among 49 other patients. These disappointing Phase II trials coupled with prominent toxicities have prompted the decision to terminate further clinical testing. This report summarizes all clinical observations as an example of circumstances which curtail clinical testing of anticancer drugs.

Aldehydes↗
PubMed1980

General progress in clinical chemotherapy of advanced disease.

Advanced cancer, because of its accompanying tumor burden, complex adverse host effects, and cellular heterogeneity, will prove much more difficult to control successfully than grave infectious diseases such as tuberculosis. This will likely be so, even when moderately successful chemotherapy is or will be available. Nevertheless, prospects for improving current results are present through application of chemotherapy alone or in combination with other modalities. Important developments include not only the availability of an increasing number of effective drugs, but also a better understanding of drug pharmacology, prediction of tumor cell cytotoxicity, locoregional drug delivery, exploitation of interactions with other forms of local therapy, and delineation of immunologic factors in tumor control. The single, most likely contribution to a curative approach to cancer, however, is likely to emerge from the application of aggressive systemic treatment in the circumstances of minimal residual disease. This topic is covered elsewhere.

Antineoplastic Agents↗
PubMed1980

N-(Phosphonacetyl)-L-aspartate (PALA): current status.

N-(Phosphonoacetyl)-L-aspartate (PALA) is a synthetic antimetabolite exhibiting striking oncolytic properties against a wide variety of experimental solid tumors. The clinical dose-limiting factor is mucocutaneous toxicity which is reversible and dose-related. Delineation of the single-agent activity of PALA in human cancer must still await results of recently activated trials.

Animals↗
PubMed1980

Clinical implications of cisplatin pharmacology.

Extensive investigation is taking place to overcome the nephrotoxic manifestations and the gastrointestinal intolerance of cisplatin. Various modes of administration are being explored for this purpose with different schedules, infusion durations, hydration programs, and diuretic regimens. Pharmacokinetic studies suggest that such manipulations may lead to considerable variations in cisplatin excretion and in peak plasma levels of the non-protein-bound species. The clinical impact of these pharmacokinetic alterations is not currently apparent. This should be clarified with additional studies of the behavior of non-protein-bound platinum and its relationship to clinical efficacy and toxicity.

Animals↗
PubMed1980

Cisplatinumdiamminodichloride (CPDD) in chemotherapy of cancers: a phase II therapeutic trial.

We have conducted a phase II trial of cisplatinumdiamminodichloride (CPDD) which not only demonstrated its remarkable activity in embryonic carcinoma of the testes, but also in ovarian carcinoma, in melanoma, and in epidermoid carcinoma, especially of the head and of the uterus cervix. Its toxicity, manifested mainly in the digestive and renal tracts, confines its administration to hospitalized patients only. This compound is now indicated in combination therapy for the above-mentioned tumors.

Adolescent↗
PubMed1980

Preclinical and phase I studies of malonatoplatinum.

After preclinical toxicologic study in baboons, we are conducting a phase I trial of malonatoplatinum, starting with 3 mg/kg and now reaching 1 mg/kg. Toxicity, mainly hematologic, was mild and our study was mainly limited by poor solubility. Regressions, which have been rare in the advanced-tumor patients, have been observed in three patients considered as clinically resistant to cisdichlorodiammino-platinum (DDP). Malonatoplatinum pharmacokinetics appeared similar to those of DDP as far as total platinum is concerned.

Adolescent↗
PubMed1980

m-AMSA: a new anticancer agent.

4'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA; NSC-249992) is a new anticancer agent that has undergone extensive experimental investigation. Clinical trials have recently been initiated and current data suggest a wide spectrum of antitumor activity in human cancer.

Aminoacridines↗