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Biomedical subjects

S Marsoni

Publications and source records attributed to S Marsoni.

54 records · Page 3Linked to original sources

Process and outcome of care for patients with ovarian cancer.

The process and outcome of care for a group of patients with ovarian cancer treated over two years in two groups of Italian general hospitals were investigated. The quality of diagnostic and therapeutic measures did not substantially differ in specialised and non-specialised centres when selected indicators of quality of care were examined. Similarly, no differences in survival emerged for the two groups of hospitals. Overall results of the Italian series compared well with statistics of survival published by international centres for cancer, suggesting that when the yield of available treatments is limited both the process and outcome of care should be evaluated to obtain a reliable picture of quality of care. In the light of these results there are useful implications for planning future clinical trials and ways of caring.

Adult↗

Tiazofurin: a new antitumor agent.

Tiazofurin is an interesting drug now entering Phase I trials, with marked preclinical antitumor activity against P388 and L1210 leukemias, and the Lewis lung carcinoma. Schedule dependency favoring frequent administration has been noted. The drug has a novel mechanism of action, being metabolized to an inhibitory cofactor of inosine monophosphate dehydrogenase. Tiazofurin is widely distributed after i.v. administration exhibiting a triphasic pattern of plasma decay, with a terminal half-life of 3-16 h in the three species studied. Approximately 90% of the drug was excreted unchanged in the urine within 24 h. A significant potential for the slower release of intracellularly retained drug exists. Anticipated organ toxicities based on the studies described include myelotoxicity, hepatotoxicity and nephrotoxicity. These were mild and reversible at lower doses, and were not seen at levels corresponding to the starting doses in man. A potential for hyperuricemia exists; this should be easily controllable by the use of allopurinol, without compromising the drug's antitumor effect. Phase I trials under the sponsorship of the NCI are underway in a number of institutions.

Animals↗

Spiromustine: a new agent entering clinical trials.

Spiromustine is a new alkylating agent, of interest since it was rationally designed as a lipophilic compound capable of penetrating the CNS. This lipophilicity may also enhance alkylating activity against tumors other than brain tumors. Preclinical screening has shown activity against a variety of tumors, including an intracranially implanted ependymoblastoma. Alkylating activity has been demonstrated in an intracerebral glioma in the rat. Spiromustine is a cell cycle non-specific agent. Animal pharmacology studies have shown a biphasic plasma decay curve, with hepatic metabolism and excretion, an enterohepatic circulation of metabolites, and approximately 50% renal excretion of unchanged drug. Toxicology studies in mice, rats and dogs showed that dose-related myelosuppression, and neurotoxicity predominated; other organ toxicities were mild. Spiromustine is currently entering Phase I clinical trials on a variety of schedules.

Alkylating Agents↗

Current status of clinical trials of m-AMSA, dihydroxyanthracenedione, and deoxycoformycin.

The current status of three drugs of clinical interest to the National Cancer Institute is reviewed. m-AMSA, a drug with a wide spectrum of activity in murine tumors, is now in phase II trial and has shown itself to have a high order of activity in acute nonlymphocytic leukemia. Dihydroxyanthracenedione, a compound with some of the characteristics of anthracyclines but with no cardiac toxicity in animal toxicology studies, is in phase I evaluation. Deoxycoformycin, an adenosine analog which is a potent inhibitor of adenosine deaminase, has shown moderate activity in acute leukemia patients in phase I trials, and has the potential to produce synergistic antitumor toxicity when used with arabinofuranosyladenine.

Adenosine Deaminase Inhibitors↗

VP16-213 and cyclophosphamide in non oat cell bronchogenic carcinoma.

Thirty-two patients with by non oat cell bronchogenic carcinoma were admitted to a protocol including Cyclophosphamide (CTX) 1,000 mg/m2 i.v. day 1, VP16-213 200 mg/m2 p.o. day 1-3, every 3 weeks. Partial remissions were seen in 2 of 27 evaluable patients; 16 of 27 showed no change. Mean survival was 36.4 weeks, median survival was 38 weeks.

Carcinoma, Bronchogenic↗

Bis-diketopiperazine derivatives in clinical oncology: ICRF-159.

ICRF-159 is a bis-diketopiperazine derivative active in a variety of preclinical animal tumor models. Because of its poor solubility characteristics, the drug must be given p.o. However, when given by this route at high doses, poor bioavailability was noted. Two interesting preclinical properties of this agent are its antimetastatic effect and the ability to reduce anthracycline cardiotoxicity. Phase I studies have delineated myelosuppression as the major toxicity with GI toxicity also occurring. In phase II studies, interesting activity has been noted in lymphomas and head and neck carcinomas. When ICRF-159 was combined with radiotherapy, prolonged responses were noted in sarcoma and lung carcinoma in small numbers of patients. Further studies are indicated in areas of activity as a single agent and as a potentiator of radiation therapy.

Animals↗

Plasma levels of cyclophosphamide in patients under polychemotherapeutic regimens.

Plasma levels of non metabolized CPA were measured in two groups of lung cancer patients receiving polychemotherapy. There was extreme variability in the data obtained during the first hour after CPA administration. After this period of time a wide range of T 1/2 was found particularly in one of the two groups of patients. "Border-line" patients (with T 1/2 at the upper or lower limits of the range found) are discussed as regards the possible influence of ancillary treatment.

Adult↗

Randomized single-agents trials in recurrent epithelial ovarian cancer.

The response to salvage treatment in recurrent epithelial ovarian cancer (REOC), is influenced by many biologic features which should be taken into account in the process of therapeutic decision. Until recently, single agents have been considered effective as combination chemotherapy in REOC and they still represent an option for well-defined categories of patients. In clinical practice, the selection of drugs for second-line treatment can be based on the knowledge that tumor size and response to prior platinum are predictors of response and that the efficacy of some commonly used single agents is supported by well designed clinical studies. Only two single-agent randomized studies with long-term survival analyses have been published; in the topotecan versus paclitaxel study, performed on a total of 235 patients, the long-term survival results did not confirm the initial report of a superiority of topotecan, with a median survival of 63 weeks and 53 weeks for patients treated with topotecan, and, respectively, paclitaxel. No comparative data were provided in the subgroup of potentially platinum-sensitive disease. In the phase III study of pegylated liposomal doxorubicin versus topotecan, into which 474 patients were treated between 1997 and 1999, the higher efficacy of pegylated liposomal doxorubicin was even more evident in the long-term survival analysis, with a 18% reduction in the risk of death, in the overall population which increased to 30% in the subset of platinum-sensitive patients. The survival after the two treatments, however, was not different in the group of patients with platinum-refractory disease. The toxicity profile of the two drugs was completely different, with palmar-plantar erythrodysestesia as most common adverse event after pegylated doxo (35% of patients) and severe neutropenia after topotecan (77% of patients). These data confirm the role of pegylated liposomal doxorubicin in the management of REOC and indicate that the identification of new active drugs in this disease is relevant but also feasible only in platinum-sensitive patients.

Antineoplastic Agents↗

Early phase pharmacokinetics of doxorubicin (adriamycin) in plasma of cancer patients during single- or multiple-drug therapy.

Doxorubicin (Adriamycin [AM]) was measured in plasma in the early distributive phase in 26 patients with different solid tumors. Pharmacokinetic parameters were calculated during first and/or subsequent courses of AM injected iv at doses from 40 to 60 mg/m2 either alone or with other antineoplastic agents. A fluorimetric technique was employed to determine AM equivalents; the reduced metabolite Adriamycinol was quantitated by scanning fluorescence after separation in thin-layer chromatography. The following conclusions are drawn from the findings. (a) After repeated AM treatments the individual variability in pharmacokinetic parameters of the drug did not appear to be affected by the length of treatment. (b) When the same patient was given different AM doses over a certain period some degree of dose dependence was seen only in the area under the curve and extrapolated plasma drug concentration at Time 0. (c) A narrow range of AM doses gave pharmacokinetic values differing from one patient to another. (d) After repeated AM treatments, Adriamycinol levels became lower, suggesting either a reduced metabolism of the parent compound or increased excretion of the reduced metabolite.

Adult↗