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Biomedical subjects

R S Benjamin

Publications and source records attributed to R S Benjamin.

At least 235 records · Page 13Linked to original sources
PubMed1978

Disposition and metabolism of 1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) in humans.

The pharmacology of high-dose 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) has been studied by radiochemical and chromatographic techniques in eight patients. Plasma disappearance of FT was exponential, with a half-life of 8.8 hr. Plasma concentrations of 5-fluorouracil (FUra) were sustained at 12.8 nmol/ml (1.7 microgram/ml) for at least 48 hr after FT administration. The concentrations of FUra derived from the administration of FT were considerably greater than were those achieved by constant infusion of FUra at the maximal tolerated dose of 1.1 g/sq m without causing unacceptable mucositis. The cumulative urinary excretion was 20% of the administered dose in 24 hr. FT underwent in vivo biotransformation to 2 hydroxytetrahydrofuranyl-5-fluorouracil derivatives in addition to anabolites and catabolites of FUra. High concentrations of FT and FUra were present in the cerebrospinal fluid, which could account for the severe central nervous system toxicity of FT at high doses. We conclude that the antitumor activity of FT is partially attributable to its slow release of FUra.

Animals↗
PubMed1978

Clinical phase I-II study of cis-dichloro-diammineplatinum(II) given by continuous lv infusion.

To determine the efficacy and toxicity of cis-dichlorodiammineplatinum(II) (DDP) by a continuous iv infusion (CIVI) schedule, 34 patients with a variety of solid tumors were studied. All patients were refractory to prior chemotherapy and received a loading dose of 5 mg/m2 of DDP iv followed by 20 mg/m2 by CIVI daily for 5 days. In 25 evaluable patients, there were four (16%) complete or partial responders, nine (25%) with stable disease, and 12 (48%) with tumor progression. One complete and one partial remission were seen in two patients with disseminated basal cell carcinoma, with partial responses also seen in cervical and head and neck squamous cancer. Patients experienced renal damage (21%) and audiotoxicity (10%). Nausea and vomiting was severe in only 6%. DDP by CIVI appears to have comparable toxicity to DDP administered by other schedules; however, the diminished gastrointestinal toxicity makes the drug better tolerated by patients for whom the inconvenience of a 5-day hospitalization is less than that caused by the nausea and vomiting of rapid infusion programs.

Cisplatin↗
PubMed1978

QRS voltage change with adriamycin administration.

A decrease in the electrocardiographic limb lead QRS voltage of greater than or equal to 30% was highly correlated with the development of congestive heart failure in patients treated with adriamycin (ADM). It is felt that if a decrease in limb lead QRS voltage greater than or equal to 30% were detected in a patient receiving ADM, cardiomyopathy might be avoided or ameliorated by discontinuation of the drug.

Adolescent↗
PubMed1978

Glycerol: a successful alternative to dexamethasone for patients receiving brain irradiation for metastatic disease.

Thirty-three patients with metastatic brain neoplasms of various types received glycerol instead of corticosteroids during periods of brain irradiation. In the 25 symptomatic patients, responses from this treatment were seen in those patients whose primary symptom was vomiting (ten of 12 patients), headache (nine of ten), papilledema (five of nine), paralysis (six of eight), confusion (six of seven), and dysphasia (four of six). Glycerol was well tolerated; it did not induce immunosuppression when administered in combination with radiotherapy and chemoimmunotherapy. Further investigation is indicated to compare its efficacy with that of dexamethasone.

Brain Neoplasms↗
PubMed1977

Adriamycin cardiomyopathy--risk factors.

The records of 53 patients treated with Adriamycin, 17 of whom developed congestive heart failure and 36 of whom received a similar total dose of Adriamycin without developing congestive heart failure, were analyzed for factors associated with Adriamycin cardiomyopathy. The risk of cardiomyopathy was significantly greater in patients who developed a larger than or equal to 30% decrease in limb-lead QRS voltage. Concurrent cyclophosphamide and mediastinal radiotherapy lowered the cumulative Adriamycin dose necessary for the development of cardiac toxicity. Uncontrolled hypertension also appears to be a risk factor in potentiating the development of Adriamycin cardiomyopathy at lower doses. Congestive heart failure was more likely to be fatal if it developed shortly after the last dose of Adriamycin. These findings can be utilized to increase the safety of Adriamycin therapy in the future.

Adolescent↗
PubMed1977

Bilary disposition of adriamycin.

A patient with a choledochal T tube and normal liver function received adriamycin as therapy for abdominal histiocytic lymphoma. Plasma, urine, and bile samples were collected after drug administration. Adriamycin and its metabolites were extracted from the samples and separated by thin-layer chromatography. The pharmacokinetics of adriamycin and metabolites in plasma urine resembled those of previous patients, with a plasma elimination half-life for adriamycin of 25.2 hr. Bile contained adriamycin and 11 metabolites, 4 of which were not present in plasma or urine. Forty-one percent of the administered dose of adriamycin appeared in the bile in 7 days; of this amount, 42% was adriamycin, 22% was adriamycinol, the major metabolite, and 36% was other metabolites. Hepatic clearances of adriamycin and adriamycinol showed early, rapid removal of drug by the liver, with subsequent slowing of removal rate as plasma drug concentration declined. Adriamycin was more efficiently cleared than adriamycinol by both liver and kidney. Disease states which impair the capacity of the liver to excrete adriamycin may result in prolonged, high drug levels and increased toxicity.

Adult↗
PubMed1977

Phase 2 study with Baker's Antifol in solid tumors.

One hundred thirty-eight adults with advanced cancers were treated with Baker's Antifol. The complete response + partial response rate was only 10%. Best responses were obtained in 31 patients with lung adenocarcinoma (complete response + partial response, 13%), in 25 patients with colorectal carcinoma (partial response, 16%), and in 6 patients with renal cell carcinoma (partial response, 50%). Two partial responses occurred in 15 patients with squamous cancer. No significant responses were seen in 27 patients with other adenocarcinomas, 13 with sarcomas, 14 with melanomas, and 8 with miscellaneous tumors. The most frequent toxicities were dermatitis, stomatitis, gastrointestinal symptoms, and mild myelosuppression. The incidence of dermatitis was significantly decreased by shortening the schedule of Baker's Antifol administration from 5 to 3 days. Baker's Antifol has some degree of antitumor activity, and studies of combination of this agent with other effective chemotherapeutic agents are indicated.

Adenocarcinoma↗
PubMed1977

Chemotherapy for metastatic carcinoid tumors: experiences with 32 patients and a review of the literature.

An analysis of results of chemotherapy in 32 patients with metastatic carcinoid tumors was carried out. The most frequently used chemotherapeutic agent was 5-fluorouracil (5-FU) followed by nitrosoureas in combination with 5-FU or with cyclophosphamide. Adriamycin (used as adriamycin-DNA complex) alone or in combination with other drugs was used in seven patients. Seven partial responses were observed, five of them occurring in the patients receiving adriamycin-containing regimens. Based on these findings, adriamycin deserves further evaluation in metastatic carcinoid tumors.

Adult↗
PubMed1977

Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function.

A new, nondestructive, plasma extraction technique ultilizing chloroform:isopropyl alcohol (1:1) and ammonium sulfate saturation has been devised to isolate adriamycin and its metabolites from human plasma. Adriamycin was the most prominent species in plasma. It disappeared according to a triphasic pattern with a mean half-life of 30 hr. Six metabolites have been clearly separated from adriamycin by thin-layer chromatography. Three were aglycones and three were polar metabolites, one of which has been identified as adriamycinol. All metabolites appeared rapidly in plasma and disappeared according to a biphasic or tri-phasic pattern. The polar metabolites in plasma were found in similar relative concentration to those in urine. In contrast to the small Quantities of aglycones in urine, however, significant concentrations of aglycones were found in plasma. The least prominent metabolite was adriamycin aglycone; the most prominent metabolite was a less polar aglycone, most likely deoxyadriamycin aglycone, and a more polar aglycone, presumably demethyl deoxyadriamycinol aglycone, was the only metabolite to show variable pharmacokinetics in different patients. The nondestructive plasma extraction technique has verified the presence of extensive human metabolism of adriamycin and demonstrated the presence of aglycone and polar metabolites.

Doxorubicin↗
PubMed1977

Nononcologic disease in patients with cancer.

Nononcologic medical problems are common in patients with cancer. Failure to evaluate and treat these problems leads to considerable morbidity and mortality in people who often have potential for both comfortable and productive lives. While a physician is sometimes powerless to prevent the progression of underlying cancer, he must not allow a diagnostic category to color his approach. By seeing only an end point which is inevitable for all people, one could be inclined not to treat what is treatable. With clinical judgment, information and the eternal question of diagnosticians, "What else could this be?", a physician can focus not on the inevitability of death but on the quality of life.

Diagnosis↗
PubMed1977

Phase II trial of Baker's antifol in metastatic sarcoma.

Iv Baker's antifol (BAF) (250 mg/m2/day X 3 consecutive days) was administered to 34 patients with metastatic sarcoma. All patients had received extensive prior therapy including prior chemotherapy and had progressive disease at the start of the study. Liver and renal functions were normal in all patients. Of 29 patients evaluable for response, 25 demonstrated progressive disease and four had stable disease for periods of from 1 to 6 months. No objective responses were observed. The other five patients died from 3 to 12 days after initiation of therapy. Toxicity included myelosuppression of significant degree in nine patients, gastrointestinal effects of nausea and vomiting in seven, stomatitis in three, and dermatitis in four. Most toxicity was mild to moderate, although one drug-related death due to marked myelosuppression was seen. In conclusion, BAF is considered to be insignificantly active in the secondary treatment of metastatic sarcomas at the dose and schedule studied.

Antineoplastic Agents↗
PubMed1976

A comparison of cyclophosphamide, vincristine, and prednisone (COP) with nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) in the treatment of nodular, poorly differentiated, lymphocytic lymphoma.

This study was designed to test the efficacy and toxicity of COP (cyclophosphamide, vincristine, and prednisone) and MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine) in 13 previously untreated patients with disseminated, nodular, poorly differentiated, lymphocytic lymphoma, and to test for patient cross-resistance to the regimens. Complete remission was initially achieved in six of eight patients on COP and three of five on MOPP. Three patients were crossed over to the alternative induction regimen because of progressive disease after an initial partial response; one was crossed over because of toxicity. On crossover, four patients achieved complete remission, two on either regimen. Durations of unmaintained complete remission range from 6-46+ months, with 8/13 still in their first complete remission. Only one patient has died, while in remission, from progressive Kaposi's sarcoma; one was lost to follow-up while in complete remission at 44 months; the others (85%) remain alive 33-54 months from the initiation of chemotherapy. MOPP was significantly more toxic with respect to thrombocytopenia, duration of myelosuppression, and cumulation of toxicity. Because of its more acceptable toxicity, COP is recommended as initial therapy for patients with nodular, poorly differentiated, lymphocytic lymphoma. MOPP or another regimen of non-crossresistant combination chemotherapy would be more appropriate for primary treatment failures.

Adult↗