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Biomedical subjects

S Fine

Publications and source records attributed to S Fine.

At least 55 records · Page 3Linked to original sources
PubMed1990

Comparison of antiestrogen and progestogen therapy for initial treatment and consequences of their combination for second-line treatment of recurrent breast cancer.

A randomized clinical trial involving postmenopausal patients with estrogen receptor positive recurrent breast cancer is reported. Of 168 patients entered, 156 were evaluable, of whom 79 received oral tamoxifen citrate 10 mg twice daily and 77 oral megestrol acetate 40 mg four times a day. Partial response (PR) plus complete response (CR) rates (both arms, 34%) and time-to-disease progression were similar in both arms. Side effects and toxicity were minimal with both regimens, although more patients who received tamoxifen complained of hot flushes (33% v 11%) and more patients who received megestrol acetate had a 10% or greater weight gain at 6 months from baseline (51% v 19%). On progression of disease, 73 patients who had achieved a CR, PR, or stable response received the alternative hormonal treatment in addition to the original hormonal therapy. Ten of 40 patients (25%) who began treatment with megestrol acetate had a further CR or PR; none of 33 patients originally receiving tamoxifen had a response when megestrol acetate was added. Similarly, patients who received tamoxifen as an addition to their original megestrol acetate treatment also had a significantly longer time to second progression than did those in the comparative arm. It was concluded that as initial hormonal therapy for relapsed patients, either tamoxifen or megestrol acetate can be used with confidence. However, it is suggested that tamoxifen and megestrol acetate should not be used in combination, except for those few occasions when tamoxifen is added as second-line therapy following a completed megestrol acetate response, and the megestrol acetate is continued for its palliative effects on appetite and weight gain. Possible mechanisms behind these results are discussed.

Breast Neoplasms↗
PubMed1989

Short-term group therapy with depressed adolescent outpatients.

A selected review of the literature about short-term therapy and social skills as they may apply to depressed adolescents is presented. Two forms of group therapy are described. These are social skills and a traditional discussion group format. Some of the difficulties in establishing and evaluating a group therapy program are outlined.

Adolescent↗
PubMed1989

Active drug placebo trial of methylphenidate--a clinical service for children with an attention deficit disorder.

A clinical trial of methylphenidate/placebo on 39 patients is described. Fifteen of 20 parents not keen to give their child methylphenidate did give it, after the trial had shown it was effective. Five out of 19 parents keen to give their child methylphenidate were persuaded not to after it was shown that it was ineffective. Some of the difficulties with the trial are described for example, parents confusing the days the drug is to be given, parents and teachers not filling in the questionnaires and the resistance of certain professionals to giving medication. Patients seem to be more accepting of recommendations to give medication or not, after a medication/placebo trial demonstrated efficacy or lack of efficacy.

Attention Deficit Disorder with Hyperactivity↗
PubMed1988

A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma.

We determined the therapeutic effect of fluorouracil (5-FU) in combination with folinic acid (FA) in patients with measurable recurrent or metastatic carcinoma of the colon or rectum by comparing it to standard 5-FU therapy in a prospective randomized controlled trial. Patients were randomized to receive either FA, 200 mg/m2/d for five consecutive days, or nothing. All patients received 5-FU, 370 mg/m2/d for five days on the first course, with subsequent dose modifications to maintain equal toxicity in the two arms. One hundred thirty patients were entered on trial and only five were excluded from the analysis because they did not meet the eligibility criteria or they refused therapy after randomization. The two treatment arms were balanced for 11 clinical characteristics. Patients were evaluated for response at the end of every two treatment courses and toxicity after every course of therapy. Median follow-up was 1.45 years. Dose-limiting toxicity was mucositis and diarrhea on this treatment schedule, although neutropenia was apparent. The response rate was 33% (21 of 63 patients) in the 5-FU and FA arm and was 7% (four of 61 patients) in the 5-FU arm (P less than .0005). Time to disease progression was significantly different in the combination arm as compared with the single-agent arm (P = .023). Overall survival was significantly longer for patients treated with 5-FU and FA as compared with those receiving 5-FU alone (P = .05). The median survival was 12.6 months for patients receiving the combination, and 9.6 months for those receiving 5-FU alone. Our results indicate that the combination of 5-FU and FA is effective treatment for patients with metastatic or recurrent carcinoma of the rectum and colon who have not received prior chemotherapy.

Adenocarcinoma↗
PubMed1988

A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer.

This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and fluorouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P approximately 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales were used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Disposition of cyclophosphamide on two consecutive cycles of treatment in patients with ovarian carcinoma.

The disposition of cyclophosphamide was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, doxorubicin (adriamycin) 50 mg/m2 and cisplatin 50 mg/m2 during their first and second courses of therapy. Plasma samples were obtained over 24 h following the completion of the cyclophosphamide infusion and assayed for cyclophosphamide by high performance liquid chromatography. The mean disposition of cyclophosphamide conformed to a 2-compartment model with a mean terminal half-life of 7.14 h on the first course and 8.77 h on the second course. Mean area under the plasma concentration versus time curve appeared to increase from 248.8 mg.h/l for the initial course to 282.2 mg.h/l on the second. Mean total body clearance was 2.01 l/h/m2 on the first course and 1.77 l/h/m2 on the second. Volume of distribution on the first and second courses were 15.3 l/m2 and 18.1 l/m2, respectively. These results suggested that cyclophosphamide clearance decreased when given in a bolus fashion every 3 weeks. However, inter-patient and intra-patient variability was large and the differences in the calculated parameters were not statistically significant when the individual patient data was considered. It is concluded that: 1. cyclophosphamide disposition can best be fit by a bi-exponential equation; 2. considerable intra- and interpatient variability in the concentration-time profile will be encountered; 3. cyclophosphamide disposition does not change from the first to the second course. Reasons for the wide variation are proposed.

Adult↗
PubMed1987

Disposition of total and free cisplatin on two consecutive treatment cycles in patients with ovarian cancer.

The disposition of total and ultrafilterable cisplatin was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cisplatin 50 mg/m2 during their first and second course. Plasma samples were obtained over 96 h following the completion of the cisplatin infusion and assayed for total platinum by atomic absorption spectroscopy. Plasma samples obtained up to 4 h after cisplatin infusion contained measurable ultrafilterable (free) cisplatin. The mean disposition of free cisplatin conformed to a two-compartment model with a mean terminal half-life (+/- SD) of 46.2 +/- 20.2 min during the first course and 37.8 +/- 18.0 min during the second course of therapy. The mean disposition of total cisplatin conformed to a three-compartment model with a mean terminal half-life (+/- SD) of 57.8 +/- 19.3 h during the first course and 86.6 +/- 33.3 h during the second course of therapy. We found that the mean total cisplatin levels were significantly higher during the second course than the first course and the total body clearance of total platinum decreased from the first to the second course. Divided urine collections were obtained over 24 h after completion of cisplatin infusion, but cisplatin was not always detectable at all time intervals. The total fraction recovered was 0.14 and 0.12 of administered dose after the first and the second course, respectively. Renal clearance was 0.61 +/- 0.32 l/h/m2 and 0.45 +/- 0.16 l/h/m2 for the first and the second course, respectively. We conclude that: urinary platinum excretion is variable between patients and with time; a trend to decreased renal clearance of platinum from first to second course may be due to a decrease in renal excretion of cisplatin; and the body's elimination pathways clear less platinum upon repeat administration.

Adult↗
PubMed1987

Computed tomography in advanced ovarian cancer: an evaluation of diagnostic accuracy.

The authors have investigated the diagnostic accuracy of computed tomography (CT) of the abdomen and pelvis in the assessment of patients prior to second-look laparotomy for advanced ovarian cancer. CT studies (read independently by three radiologists) and laparotomy findings were analyzed in 50 patients. Sensitivity varied from 0.30 to 0.65 among the radiologists, specificity from 0.44 to 0.89, positive predictive value from 0.50 to 0.73, and negative predictive value from 0.60 to 0.70. Receiver operator curve analysis of the data indicated poor performance of CT as a diagnostic test. The authors also examined some problems in interpreting their data and that of others in the literature, in particular, the influence of potential sources of bias.

Evaluation Studies as Topic↗
PubMed1987

Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma.

The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two-compartment linear model in 21 of 25 courses monitored with a mean t1/2 lambda 1 of 9.8 +/- 1.2 (SEM) min and mean t1/2 lambda z of 64.1 +/- 8.9 (SEM) min. The large variation observed in t1/2 lambda z was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t1/2 lambda z or the area under the curve. This may be due to a failure to monitor active metabolites of mitomycin C; other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or the small number of courses associated with thrombocytopenia (less than 100,000/mm3). Our study indicates that an interaction of drug dose and treatment course may be associated with increasing t1/2 lambda z; the renal clearance contributes a small component of mitomycin C elimination; metabolites of mitomycin C cannot be detected by the present HPLC technique; and routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity.

Aged↗
PubMed1987

Two Japanese families: a cultural perspective.

Some of the difficulties in treating second and third generation Japanese immigrant families are reviewed. An authoritarian, rather concrete approach to symptom relief is expected by, and is effective in, some families. The emphasis placed on academic achievement may lead to particular problems and misunderstandings. Two case examples of very different families are presented to emphasize a flexible therapeutic approach. Particular details of Japanese internment and population movements make the attitudes and behaviors of some families more comprehensible.

Acculturation↗
PubMed1987

A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.

One hundred ninety-two patients with previously untreated metastatic cancer (102 non-small-cell lung cancer [NSCLC]; 90 colorectal cancer) were randomized to receive either ad lib nutritional intake (control group) or specific nutritional intervention during a 12-week study period when chemotherapy was administered. Those patients randomized to nutritional interventions were counselled to take oral nutrients with caloric intake equal to 1.7 to 1.95 times their basal energy expenditure, depending on their pretreatment nutritional status ("standard" group). An augmented group was counselled to have a caloric intake equivalent to that of the standard group but with 25% of calories provided as protein and additional supplements of zinc and magnesium. Counselling increased caloric intake in both tumor types but reduced weight loss in the short term only for lung cancer patients. Ninety-three NSCLC patients were evaluable for tumor response to vindesine and cisplatin. Overall, only 20.4% of the patients responded, and there were no significant differences in response rates, median time to progression, or overall duration of survival between the nutrition intervention groups and the control group. The tumor response rate to time-sequenced 5-fluorouracil (5-FU) and methotrexate in the 81 evaluable patients with colorectal cancer was only 14.8%, and no significant differences in tumor response rates were noted between the three groups. Furthermore, the median time to progression and overall duration of survival were not different for the control, standard, and augmented groups. Nutritional interventions using dietary counselling had no impact on the percent of planned chemotherapy dose administered, the degree of toxicity experienced by patients, or the frequency of treatment delays. A multivariate prognostic factor analysis demonstrated that for lung cancer, the percent of weight loss, serum albumin concentration, and presence of liver metastases were significant (P less than .05) and independent prognostic variables for survival duration. For colorectal cancer, serum albumin, alkaline phosphatase, lactic dehydrogenase (LDH) levels, and percent targeted caloric intake (TCI) were significant independent predictors of survival duration.

Adult↗
PubMed1987

Hepatic arterial infusion of mitoxantrone in the treatment of primary hepatocellular carcinoma.

Twenty-three patients (16 male, seven female) with hepatocellular carcinoma (HCC) were treated by hepatic arterial infusion (HAI) of mitoxantrone every 4 weeks. At each treatment, a catheter was inserted percutaneously into the main hepatic artery via the femoral artery under image intensification. Treatment consisted of a 24-hour continuous HAI of mitoxantrone, 6 mg/m2/d X 3 (eight patients) or 10 mg/m2/d X 3 (14 patients) without heparin. Eight patients had only one infusion, nine patients four infusions, five patients three infusions, two patients two infusions, and one patient five infusions. A partial response was seen in six patients, with a median duration of 20 weeks (range, 18 to 38 weeks). Five patients achieved stable disease, with a median duration of 20 weeks (range, 11 to 42 weeks). The median survival of the overall group was 22 weeks. Survivals of responding, stable, and nonresponding patients were 32 weeks, 24 weeks, and 9 weeks, respectively. Complications of catheter placement included asymptomatic dissection of the hepatic artery (one patient), and asymptomatic thrombosis of the hepatic artery (five patients). Three patients experienced mild nausea and vomiting, and six patients had mild to moderate alopecia. Granulocytopenia was frequent at both dose schedules. The granulocyte nadir was greater than 1,000/microL in 34% of evaluable courses, 500 to 1,000/microL in 32%, and less than 500/microL in 34% of courses. Two patients developed neutropenia-associated fever. A platelet nadir below 100,000/microL was seen after only 10% of courses, and only two patients had platelets below 50,000/microL. Seven patients received doxorubicin after progression on mitoxantrone. Four received systemic doxorubicin, 50 mg/m2, and three HAI of doxorubicin, 25 mg/m2, for three days. Two patients achieved partial response (18 weeks and 32 weeks) to HAI doxorubicin. Mitoxantrone has activity in HCC and is well tolerated when administered by HAI. It is not entirely cross-resistant with doxorubicin.

Adult↗