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Biomedical subjects

S Fine

Publications and source records attributed to S Fine.

At least 19 recordsLinked to original sources
PubMed1996

A phase II trial of 5-fluorouracil and 1-leucovorin in patients with metastatic colorectal cancer.

We undertook a multicenter phase II trial of 5-fluorouracil (5FU) + 1-leucovorin (1-LV) in previously untreated patients with metastatic colorectal cancer to determine the response rate, response duration, time to progression, survival, and toxicity. Patients were treated with i.v. 5FU 370 mg/m2/day and 1-LV 100 mg/m2/day x 5 every 28 days. Toxicity and response were determined by WHO criteria. One hundred and twenty-six patients were entered, and 119 patients were eligible and evaluable. Eighty-eight patients had colon cancer and 37 had rectal cancer. The male:female ratio was 58:68. The mean age was 62.2 years. ECOG performance status distribution was 0 (39.7%), 1 (46%), and 2 (11.9%). The median number of courses of therapy administered was 4.5. Severe- or life-threatening stomatitis or diarrhea, nausea, and granulocytopenia occurred in 17.6, 23.2, 17.6, and 15.9% of patients, respectively. The response rate was 22/119 [18.5%; 95% confidence interval (CI) of 12.0-26.6]. Median response duration was 188 days (95% CI of 111-248 days). Median survival was 379 days (95% confidence interval of 289-452 days). These results indicate that when 1-LV is combined with 5FU, toxicity is similar in pattern and severity to that of the d,1 racemic mixture. The overall efficacy of 1-LV + 5FU is comparable to a recent metaanalysis.

Adult↗
PubMed1995

A clinical and pharmacological study of 5-fluorouracil, leucovorin and interferon alfa in advanced colorectal cancer.

Modulation of 5-fluorouracil (FUra) using leucovorin (LV) is a standard treatment approach in patients with metastatic colorectal cancer. Modulation of FUra with interferon alfa has also shown some promise. Laboratory data have demonstrated increased cytotoxicity when FUra is combined with both LV and interferon. The current study examined the effects of double modulation of FUra using LV and interferon. Patients with measurable advanced colorectal cancer received bolus FUra 375 mg/m2 plus LV 20 mg/m2 daily for 5 days, repeated every 28 days. Recombinant human interferon alfa-2a, 3 million IU/m2 subcutaneously, was given daily on the days of chemotherapy then three times weekly. There was one complete response and nine partial responses (10/41) seen for an overall response rate of 24% (95% CI 12.0-40.0%). Overall, 70% of patients experienced one or more episodes of nonhematologic toxicity of grade 3 or more. Weight loss was common, with a mean decrease of 2.9 kg over the first two months (P < 0.0001). Improvements in tumor-related symptoms were balanced by increased fatigue and a deterioration in body weight and performance status. There was no evidence of progressive changes in FUra metabolism from interferon usage.

Adult↗
PubMed1994

Phase II trial of 5-fluorouracil and folinic acid in the treatment of advanced breast cancer.

Standard combination chemotherapy for metastatic breast cancer produces response rates between 30-60% with limited impact on survival. We undertook a phase II trial to determine the activity of 5 fluorouracil (5FU) and folinic acid (FA) in patients with measurable metastatic or recurrent breast cancer who had received no prior chemotherapy. Patients meeting the eligibility criteria received 5FU 370 mg/m2/day and FA 200 mg/m2/day for 5 days repeated every 28 days, toxicity allowing. Response defined by standard criteria was assessed every 8 weeks and toxicity according to WHO criteria was determined on every course. Thirty-three patients were entered on trial. Thirty-two patients were evaluable for response and 33 for toxicity. The dose limiting toxicity was stomatitis with 7/32, 19/32, and 5/32 patients experiencing grade 1, 2, and 3 toxicity. Grades 1 and 2 diarrhea occurred in 17/32 and 11/32 patients respectively. Myelosuppression was not significant. Two complete and 11 partial responses were observed. The overall response rate was 41% (95% CI, 24-58%). Responses were seen in soft tissue and visceral sites. Patients who had received adjuvant chemotherapy more than 6 months prior to receiving 5FU and FA responded also. Six of 29 patients receiving standard combination chemotherapy as second line treatment responded subsequently. We concluded: 1) 5FU and FA is an active combination in the treatment of breast cancer warranting further evaluation in combination with other drugs; 2) the dose-limiting toxicity of stomatitis is tolerable; 3) patients receiving 5FU and FA as first line therapy can respond to conventional combination chemotherapy as second line treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Clinicopathologic correlation of the multiple recurrent serosanguineous retinal pigment epithelial detachments syndrome.

PURPOSE: Ocular clinicopathologic correlation in a patient with bilateral multiple recurrent hemorrhagic detachments of the sensory retina and retinal pigment epithelium (RPE), which eventually led to rubeosis and loss of useful vision in one eye, is described. The clinical appearance was most consistent with multiple recurrent serosanguineous RPE detachments syndrome (which may be similar to posterior uveal bleeding, or PUB, syndrome). METHODS: Light microscopic examination of 450 serial sections through a 3.7-mm area including the macula, optic nerve head, and superior and inferior peripapillary region of the eye that underwent diagnostic enucleation was performed. One fresh cap was used for immunohistochemical staining. Tissue from the posterior aspect of the other cap was prepared for electron microscopy. RESULTS: Microscopic examination disclosed extensive fibrovascular proliferation in the subretinal space and within Bruch's membrane, and the presence of at least 23 choroidal blood vessels that traversed defects in Bruch's membrane. Immunohistochemical studies of inflammatory infiltrates within the choroid and fibrovascular tissue demonstrated both a B- and T-cell response. CONCLUSION: In this case, recurrent serosanguineous detachments of the sensory retina and RPE were secondary to choroidal neovascularization with extensive fibrovascular proliferation in the subretinal space and within Bruch's membrane. Marked lymphocytic infiltration was present throughout the choroid and the fibrovascular tissue. Clinical improvement in the fellow eye after immunosuppressive therapy suggested that an immunologic component might be a causative factor, although the waxing and waning course in this condition precludes any definitive evaluation for its use in multiple recurrent serosanguineous RPE detachments syndrome.

Bruch Membrane↗
PubMed1994

Factors associated with dropout from group psychotherapy with depressed adolescents.

Attempts to determine the characteristics of those individuals who drop out from psychotherapy have yielded few consistent findings. Clinically depressed adolescents who completed a course of brief group therapy were compared with those who failed to complete treatment. Although no differences were found on a number of clinical and demographic variables, those who dropped out were more likely to be one grade behind in school and to have a history of alcohol and/or drug abuse. The implications of these findings for research and practice are discussed.

Adolescent↗
PubMed1993

Impact of chemotherapy-associated nausea and vomiting on patients' functional status and on costs: survey of five Canadian centres.

OBJECTIVE: To estimate the effect of chemotherapy-associated nausea and emesis on patients' functional status and on costs to the health care system, the patients and society before antagonists to the serotonin (5-hydroxytryptamine) receptor subtype 5-HT3 became available. DESIGN: A 5-day prospective survey between February and May 1991 of patients receiving chemotherapy for cancer. Data were obtained from questionnaires completed by nurses and patients. SETTING: Five Canadian cancer treatment centres in Ontario (three) and Quebec (two). PATIENTS: Outpatients and inpatients 18 years of age and older who were scheduled to receive chemotherapy with a moderate to high potential for emesis as defined by standardized criteria. Patients were excluded if they were scheduled to receive an investigational antiemetic or had received chemotherapy within the previous 7 days. Of the 128 who were eligible, 112 agreed to participate; 107 returned the completed questionnaire, but the data for 15 were excluded because the patients received multiple-day chemotherapy. MAIN OUTCOME MEASURES: The degree of nausea (on a seven-point scale) and the frequency of emesis (vomiting or retching) were recorded for each day of the survey. Functional status was assessed before and after chemotherapy by means of the Functional Living Index-Emesis (FLIE). The direct health care costs and the indirect costs (e.g., of time off work) associated with nausea and emesis were estimated from the survey responses and secondary data sources. RESULTS: On the day of chemotherapy 38 of the 92 patients (41%) experienced emesis with or without nausea, and over the 5 days of the survey 72 patients (78%) reported at least one episode of nausea or emesis. The absolute risk of either problem decreased over time, but the risk of nausea relative to emesis increased over time. The FLIE scores indicated significant worsening of functional status after chemotherapy. On the day after treatment the main impact was from emesis, particularly with regard to leisure activities, household tasks and hardship to the family. Nausea had a significantly greater impact than emesis on overall functioning. The additional direct health care cost for managing emesis was estimated to be $63 and the indirect cost $121. CONCLUSIONS: Despite prophylaxis with antiemetic drugs, nausea and emesis were significant problems in this population receiving chemotherapy. The management of emesis consumed relatively small amounts of health care resources, but there were costs outside the hospital for patients and others.

Activities of Daily Living↗
PubMed1993

Drug and placebo side effects in methylphenidate-placebo trial for attention deficit hyperactivity disorder.

In a double-blind methylphenidate placebo trial for children with Attention Deficit Hyperactivity Disorder (ADHD), side effects were reported on both placebo and methylphenidate (MPH), and many side effects were similar to the symptoms of ADHD. We suggest that parents and teachers may mistake the symptoms of ADHD for side effects of MPH, and this misconstrual may contribute to the poor acceptance of and compliance with taking MPH.

Attention Deficit Disorder with Hyperactivity↗
PubMed1993

Methods of evaluating methylphenidate in children with attention deficit hyperactivity disorder: acceptability, satisfaction, and compliance.

Compared two methods of evaluating methylphenidate (MPH) on measures of parental acceptance, satisfaction, and compliance with the treatment. Twenty-four 6- to 10-year-old children with Attention Deficit Hyperactivity Disorder (ADHD) were randomly assigned to either a blind, placebo-controlled medication trial (MT) or to a typical clinical procedures (TCP) evaluation that was nonblind and without a placebo control. Ratings of satisfaction were significantly higher in the MT condition than in the TCP condition; however, all parents became more accepting of MPH after participating in an evaluation. Both during the evaluation and at 6-week and 3-month follow-ups, approximately 20% of cases were not complying with treatment. However, rates of compliance did not differ between the MT and TCP conditions.

Attention↗
PubMed1993

A phase II study of 5-fluorouracil, leucovorin and interferon-alpha in advanced pancreatic cancer.

Increased activity against colorectal cancer by 5-fluorouracil (5-Fu) modulation with leucovorin (LV) and/or interferon (IFN) has been reported. In this study 22 patients with measurable advanced pancreatic cancer received 5-Fu 375 mg/m2 and LV 20 mg/m2 by i.v. bolus daily x 5 every 28 days plus IFN-alpha 3 million units/m2 s.c. There were three out of 21 (14%) responses lasting from 4 to 8 months. Sixteen patients (73%) had one or more episodes of grade 3 or greater toxicity (stomatitis, diarrhea or fatigue). While this combination has some activity against pancreatic cancer, its toxicity limits its potential as a palliative treatment.

Adenocarcinoma↗
PubMed1993

Self-image as a predictor of outcome in adolescent major depressive disorder.

We investigated the ability of a measure of self-image, two measures of depression, and demographic characteristics to predict the outcome of depressive symptoms. Subjects were 47 adolescents who were referred to outpatient treatment for depression. Subjects were assessed for depressive symptoms at three time periods. Self-image as measured by the Offer Self-image Questionnaire (OSIQ) was a significant predictor of depressive symptoms at both 3 months and 1 year. That was independent of initial levels of depression. The two most predictive scales from the OSIQ were the emotional tone and mastery of the external world scales. The results are consistent with previous research indicating the importance of self-image in adolescent depression. The implications of these findings for treatment of adolescent depression are discussed.

Adolescent↗
PubMed1992

Paraphilias: a double-blind crossover comparison of clomipramine versus desipramine.

A relationship has been suggested between clinical presentation of paraphilias and obsessive-compulsive disorder (OCD) with respect to the unwanted repetitive nature and insight into the irrationality of the paraphiliac behavior. This has led to speculation that paraphiliac disorders might belong to an "obsessive compulsive spectrum." To address this issue, and because of the striking selective benefit of serotonin reuptake blocking antidepressants (such as clomipramine) in the treatment of OCD, 15 paraphiliacs entered a double-blind crossover comparison of clomipramine vs. desipramine preceded by a 2-week single-blind placebo period. Four subjects responded to placebo and were dropped from the study. Three others failed to complete the study. Although the study is limited by the small number of patients and the heterogeneity of the paraphilias, the observed benefit from both tricyclics (over the initial placebo) encourages further study. For the 8 subjects completing the protocol, there was no preferential response to the more specific serotonin reuptake inhibitor suggesting a difference in underlying pathophysiology between paraphilia and OCD.

Adult↗
PubMed1992

Complications of whole abdominal and pelvic radiotherapy following chemotherapy for advanced ovarian cancer.

We examined the records of 105 patients with advanced ovarian cancer who had been treated with cisplatin combination chemotherapy followed by abdominopelvic radiotherapy. The purpose was to define the morbidity of this approach, and identify those factors predictive of toxicity. Acute toxicity resulting in delay or failure to complete treatment was most commonly due to myelosuppression. Nine of 105 patients (8.6%) required surgery for bowel obstruction that was not due to recurrent disease, 3 had an episode of bowel obstruction that settled conservatively, and a further 5 underwent surgery for obstruction due to recurrent tumor. The presence of both a dose of abdominopelvic radiotherapy over 2250 cGy, as well as a second-look laparotomy prior to radiotherapy, was associated with an increased risk of serious bowel complications. The increased frequency of late bowel morbidity seen in the combined modality group is likely explained by the presence of these two factors, rather than the exposure to chemotherapeutic agents per se. These observations are supported by the published literature.

Abdomen↗
PubMed1992

Prognostic factors in patients with metastatic colorectal cancer receiving 5-fluorouracil and folinic acid.

We have reported that 5-fluorouracil (5-FU) and folinic acid increased response rate and survival in patients with metastatic colorectal cancer. Now we have analysed prognostic factors for response, toxicity, survival and time to progression. The variables used for survival and response were treatment centre, treatment, age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), site of disease, previous radiotherapy, site of primary, disease-free interval, initial alkaline phosphatase (AP), albumin (A), lactate dehydrogenase (LDH) and aspartate aminotransferase (SGOT). The significant independent variables for survival were PS of 2 or more, initial albumin and SGOT, and treatment received, in order of importance. The relative risk of death when patients received 5-FU/folinic acid was 60% of that of patients receiving 5-FU alone. The variables predictive of response were treatment and PS. The variables used for analysis of toxicity were age, treatment centre, treatment, sex, tumour response, PS, number of courses, SGOT, AP and albumin. Treatment was found to be predictive of toxicity. Thus, baseline albumin and SGOT, and 5-FU/folinic acid treatment are significant determinants of survival, 5-FU/folinic acid and PS of 2 or more are major determinants of response and no clinical parameter could be identified as a predictor of toxicity.

Adult↗
PubMed1991

Superiority of granisetron to dexamethasone plus prochlorperazine in the prevention of chemotherapy-induced emesis.

Trials of selective 5-hydroxytryptamine3 receptor antagonists have shown excellent antiemetic activity for chemotherapy containing cisplatin when compared with high-dose metoclopramide. There is little information about the efficacy of these new agents for chemotherapy other than for high-dose cisplatin. We performed a double-blind, randomized trial comparing a single dose of the 5-hydroxytryptamine3 receptor antagonist granisetron (BRL 43694A) as a single intravenous dose with dexamethasone plus prochlorperazine in 152 patients receiving their first course of moderately emetogenic chemotherapy (mainly doxorubicin- and cyclophosphamide-containing combinations). During the first 24 hours, there was a statistically significant advantage for the granisetron group in terms of the prevention of both nausea and emesis. There was no difference in the frequency of reported adverse events. We conclude that granisetron is more effective than dexamethasone plus prochlorperazine in patients who are receiving moderately emetogenic cytotoxic agents.

Antiemetics↗
PubMed1991

Outcome of patients with unfavorable optimally cytoreduced ovarian cancer treated with chemotherapy and whole abdominal radiation.

There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despite optimal cytoreduction of tumor and abdominopelvic radiation. This study examined whether the survival of these patients, who have tumor with unfavorable histopathological characteristics and/or small residual disease, could be improved by giving chemotherapy before radiation. Forty-four out of fifty-one eligible patients, seen between 1981 and 1985, with Stage II or III disease were entered into the study. Following six courses of cisplatin-based chemotherapy, 33 (75%) received abdominopelvic radiotherapy. Survival was compared to that of 48 eligible matched control patients, treated with radiation between 1978 and 1981. The median follow-up is 6.6 years. The median survival was extended from 2.4 to 5.7 years (P = 0.13), and 42.6% of patients receiving combined therapy were free of relapse at 5 years, compared to 21.6% (P = 0.03) in the historical control group, treated with abdominopelvic irradiation alone. Only 2 of 44 patients in the combined group required surgery for bowel obstruction, as did 1 of 48 in the control group. Tolerance and toxicity of the combined approach were acceptable. Although we cannot be certain that the entire benefit we observed was not attributable to the chemotherapy alone, there is evidence that the radiotherapy may have been additive. Chemotherapy followed by abdominopelvic radiotherapy seems a reasonable management policy in these patients.

Antineoplastic Combined Chemotherapy Protocols↗