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Biomedical subjects

F M Muggia

Publications and source records attributed to F M Muggia.

At least 127 records · Page 7Linked to original sources
PubMed1988

The disposition of carboplatin in ovarian cancer patients.

Carboplatin was given as a 30-min infusion to 11 ovarian cancer patients at doses of 170-500 mg/m2. The ages, weights, and creatinine clearances (Clcr) ranged from 44 to 75 years, from 44 to 74 kg, and from 32 to 101 ml/min, respectively. Plasma, plasma ultrafiltrate (PU), and urine samples were obtained at appropriate times for 96 h and were analyzed for platinum. The PU and urine were also analyzed for the parent compound by HPLC. In patients with a Clcr of about 60 ml/min or greater, carboplatin decayed biexponentially with a mean t1/2 alpha of 1.6 h and a t1/2 beta of 3.0 h. The mean (+/- SD) residence time, total body clearance, and apparent volume of distribution were 3.5 +/- 0.4 h, 4.4 +/- 0.85 l/h, and 16 +/- 3 l, respectively. Cmax and AUCinf values increased linearly with dose, and the latter values correlated better with the dose in mg than in mg/m2. No significant quantities of free, ultrafilterable, platinum-containing species other than the parent compound were found in plasma, but platinum from carboplatin became protein-bound and was slowly eliminated with a minimal t1/2 of 5 days. The major route of elimination was excretion via the kidneys. Patients with a Clcr of 60 ml/min or greater excreted 70% of the dose as the parent compound in the urine, with most of this occurring within 12-16 h. All of the platinum in 24-h urine was carboplatin, and only 2%-3% of the dosed platinum was excreted from 48 to 96 h. Patients with a Clcr of less than about 60 ml/min exhibited dose-disproportional increases in AUCinf and MRT values. The latter were inversely related to Clcr (r = -0.98). Over a dose range of 300-500 mg/m2, carboplatin exhibited linear, dose-independent pharmacokinetics in patients with a Clcr of about 60 ml/min or greater, but dose reductions are necessary for patients with mild renal failure.

Adult↗
PubMed1988

Treatment of epidemic Kaposi's sarcoma with a combination of interferon-alpha 2b and etoposide.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer.

Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Lethal and sublethal effects of the combination of doxorubicin and the bisdioxopiperazine, (+)-1,2,-bis (3-5-dioxopiperazinyl-1-yl) propane (ICRF 187), on murine sarcoma S180 in vitro.

Doxorubicin and the bisdioxopiperazine, ICRF 187, synergistically inhibit proliferation of murine sarcoma S180 cells in vitro. Cell cycle analysis was employed to help discriminate cytokinetic from lethal effects of the drug combination. Twenty-four-hour incubation with either agent produced dose-dependent partial G2M arrest. At high doses, ICRF 187 produced partial G2M arrest, inhibition of cell division, and continued DNA synthesis at a higher ploidy, resulting in a second G2M arrest of an 8n population. The addition of ICRF 187 to doxorubicin resulted in enhancement of cell cycle blockade at G2M. The combination also produced enhanced lethality as measured by reduced colony-forming efficiency of drug-treated S180 cells. Measurement of [14C]doxorubicin accumulation in, and effux from, ICRF 187 pretreated cells failed to reveal an effect of pretreatment with the bisdioxopiperazine on anthracycline disposition by S180 cells, suggesting that the enhanced cytotoxic and cytostatic effects do not result from increased intracellular concentrations of doxorubicin. The positive interaction between the two drugs may represent site-specific enhancement of the anthracycline effect by ICRF 187 at an intracellular target site.

Animals↗
PubMed1987

Phase II trial of oral methotrexate and dipyridamole in colorectal carcinoma.

We have employed a rationally designed combination attempting to biochemically modulate the cytotoxicity of methotrexate (MTX), an inhibitor of de novo purine and pyrimidine synthesis, by dipyridamole (DP), a noncytotoxic modulator which blocks cellular transport of preformed nucleosides, in the treatment of 27 patients with advanced colorectal carcinoma. Doses and schedule determined from a previous phase I pharmacokinetic study were MTX at 2.5 mg orally twice a day for 4 days to begin concurrently with DP, at 75 mg orally four times daily for 8 days. One partial response was achieved in a patient who had progressed on a previous regimen of leucovorin and 5-fluorouracil. The major toxic effects observed were myelosuppression and stomatitis. Lack of efficacy could be interpreted to reflect incomplete modulation. Therefore, studies employing continuous iv infusion of DP concurrent with or a loading schedule of DP prior to administration of MTX may be required to provide adequate evaluation of such biochemically directed strategies.

Adenocarcinoma↗
PubMed1987

Surgical treatment for advanced epithelial carcinoma of the ovary.

The three surgical steps in the management of carcinoma of the ovary--staging laparotomy, cytoreductive operation and second-look laparotomy--must be critically re-evaluated. During the past decade much data has been assembled on platinum based combination chemotherapy. The results of this type of chemotherapy questions the importance of these procedures. Whereas staging laparotomy will continue to determine important issues in the management of early disease, the use of cytoreduction and second-look laparotomy must be questioned as a routine or important determinant of current treatment results.

Carcinoma↗
PubMed1987

Weekly 5-fluorouracil combined with PALA: toxic and therapeutic effects in colorectal cancer.

A total of 51 patients (eight previously treated) received PALA added to 5-fluorouracil (5FU) given weekly. After 32 patients, the PALA schedule was changed from every other week to weekly, 24 hours preceding 5FU in accordance with preclinical leads (see text). Both schedules were associated with moderately severe toxic effects related primarily to PALA (skin rash) or to the combined effects of both drugs (diarrhea, vomiting, conjunctivitis, and neurotoxicity). Overall nine partial responses were observed, including three in patients previously treated with 5FU. However, future studies with this combination utilizing the current or other previously published schedules are not warranted in colorectal cancer. Since toxicity is a prominent impediment, the possibility of therapeutic synergy may perhaps be explored at drastically reduced doses of PALA, combined with other modulating measures.

Adult↗
PubMed1986

Kaposi's sarcoma and AIDS.

Mucocutaneous lesions are often a prominent manifestation of the acquired immune deficiency syndrome (AIDS). Patients with this syndrome are susceptible to a number of opportunistic skin infections as well as an aggressive form of Kaposi's sarcoma. The diagnosis, the clinical setting, and the treatment of these diseases are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Synergistic activity of doxorubicin and the bisdioxopiperazine (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187) against the murine sarcoma S180 cell line.

The bisdioxopiperazine (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)-propane (ICRF 187) abrogates doxorubicin cardiotoxicity in every mammalian species tested, but its effect on doxorubicin antitumor activity remains poorly understood. In order to better define the anthracycline-bisdioxopiperazine interaction, the ability of murine sarcoma S180 cells to form colonies in soft agar and their capability to proliferate in microtiter wells were assayed after exposure to drug at varying doses and schedules. Incubation of cell suspensions for 1 h with doxorubicin, 0.1 microgram/ml, with or without (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane, 80 micrograms/ml, produces additive cytotoxicity for the combination. Prolonged incubation (24 h) with the same drugs produces synergistic cytotoxic and antiproliferative effects at 1- and 2-log order reductions in dose. These studies indicate that the antineoplastic activity of the single agents doxorubicin and (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane is enhanced when the drugs are used in combination, and that this phenomenon is highly dose and schedule dependent.

Animals↗