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Biomedical subjects

R J Forcier

Publications and source records attributed to R J Forcier.

At least 19 recordsLinked to original sources
PubMed1990

Lack of acute toxicity associated with a multimodality treatment of stage III ovarian epithelial carcinoma.

Eleven patients with advanced stage III ovarian epithelial carcinoma were treated primarily according to an aggressive multimodality plan utilizing cytoreductive surgery, chemotherapy (high-dose cisplatin and Cytoxan), and consolidative radiation therapy (abdominopelvic "bath" plus pelvic boost). The treatment was tolerated remarkably well. There was no evidence of progressive disease during treatment, and all patients showed a positive response. There was a notable lack of significant acute morbidity, with the exception of a severe symptomatic peripheral neuropathy associated with cisplatin doses of 200 mg/m2. This was not evident with doses of cisplatin up to 150 mg/m2.

Adult↗
PubMed1988

Effect of mopidamol on survival in carcinoma of the lung and colon: final report of Veterans Administration Cooperative Study No. 188.

Mopidamol (RA-233), a derivative of dipyridamole, is a phosphodiesterase inhibitor that has been shown previously to limit progression of malignancy in certain experimental animal models and in a pilot study in humans. RA-233 plus chemotherapy was compared with chemotherapy alone in a 5-year double-blind trial involving 719 patients with advanced carcinomas of the lung and of the colon. RA-233 treatment was associated with a statistically significant prolongation of survival in patients with non-small cell lung cancer (N-SCLC) limited to one hemithorax and with reduction in mean plasma fibrogen concentration. RA-233 was not toxic. The favorable effects on survival could not be explained by any factor other than the RA-233 treatment. In other tumor categories tested, no differences in survival were observed. These results suggest that RA-233 is useful in the treatment of N-SCLC of limited extent. They also suggest that therapeutic intervention aimed at modified intracellular pathways might constitute a novel investigative approach to the treatment of cancer.

Carcinoma↗
PubMed1987

Abnormalities of blood coagulation tests in patients with cancer.

Routine blood coagulation tests were performed on 431 consecutive patients enrolled in a study of the role of anticoagulation in cancer treatment (VA Cooperative Study #75). Two hundred sixteen control patients were treated with standard therapy, and 215 patients were treated with standard therapy plus sodium warfarin. At the time of entry into the study, the most common abnormalities were elevated fibrinogen levels, platelet counts, and fibrinopeptide A levels. Serial studies demonstrated a steady increase in platelet count and fibrinogen levels before death. Anticoagulation lowered FPA levels but had no significant effect on fibrinogen levels, platelet counts, or euglobulin clot lysis times. An unexpected finding was a dramatic increase in fibrin split product levels after institution of anticoagulation (means +/- SEM = 42.6 +/- 116.4 vs. 2.9 +/- 7.0 mg/L in control subjects; P less than 0.02). This study supports the presence of subclinical activation of blood coagulation in most patients with cancer. Moreover, the preferential activation of fibrinolysis in anticoagulated patients suggests a role for a vitamin K-dependent factor(s) in the regulation of fibrinolysis in patients with cancer.

Blood Coagulation Tests↗
PubMed1985

Bleeding complications from warfarin anticoagulation in patients with malignancy.

Bleeding complications from warfarin anticoagulants were analyzed in 431 patients with carcinoma of the lung, colon, prostate and head and neck who were admitted to a randomized, controlled therapeutic trial of this agent. A total of 215 patients were randomized to the warfarin-treated group and 216 to the control groups. The mean prothrombin time was significantly prolonged (p = 0.0001) for warfarin-treated patients. The duration of warfarin administration was 64.9% of the total followup period providing 101 patient-years of experience with warfarin in cancer. Both the overall incidence of bleeding episodes (58% of warfarin-treated versus 30% of control) and the incidence of major bleeding episodes (42% versus 14%, respectively) were significantly increased in the warfarin-treated group (p = less than 0.001). The incidence of major bleeding was 1.86 per patient-year on warfarin. The most common sites of bleeding (in descending order) were the gastointestinal tract, the urinary tract, the nasal passages and skin. Hemorrhage occurred in association with the terminal event in 10 warfarin-treated and 12 control patients. Warfarin anticoagulation may have contributed to terminal bleeding in 3 (1.4%) patients. There was no difference in mean hemoglobin or hematocrit values for patients with versus patients without bleeding episodes.

Clinical Trials as Topic↗
PubMed1984

Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75.

VA Cooperative Study #75 was established to test in a controlled, randomized trial the hypothesis that warfarin anticoagulation would favorably affect the course of certain types of malignancy. No differences in survival were observed between warfarin-treated and control groups for advanced non-small cell lung, colorectal, head and neck and prostate cancers. However, warfarin therapy was associated with a significant prolongation in the time to first evidence of disease progression (P = 0.016) and a significant improvement in survival (P = 0.018) for patients with small cell carcinoma of the lung, including the subgroup of patients with disseminated disease at the time of randomization (P = 0.013). A trend toward improved survival with warfarin treatment was observed for the few patients admitted to this study with non-small cell lung cancer who had minimal disease at randomization. These results suggest that warfarin, as a single anticoagulant agent, may favorably modify the course of some, but not all, types of human malignancy, among which is small cell carcinoma of the lung. Further trials of warfarin may be indicated in patients with limited disease who have cell types that failed to respond when advanced disease was present.

Adenocarcinoma↗
PubMed1984

Intensive cytosine arabinoside therapy in small cell carcinoma of the lung.

Cytosine arabinoside (Ara-C) 100 mg/m2/d was given by continuous infusion to patients with small cell carcinoma of the lung in two simultaneous studies. In a first study, 10 patients who had failed prior therapy were treated with Ara-C alone. No responses were seen in these heavily pretreated patients and toxicity was severe. In a second study, Ara-C was added to the known active combination of cyclophosphamide, adriamycin, and vincristine (CAV) in 25 patients with extensive-stage small cell carcinoma with no prior treatment. Despite a clinical response rate of 52% (28% complete remissions, 24% partial remissions), the median survival was 169 days. This aggressive therapy approach produced substantial toxicity and no therapeutic benefit over previous regimens. Continuous infusion Ara-C (100 mg/m2/d X 3 days) used alone, or combined with CAV is not a useful agent for cell carcinoma of the lung.

Aged↗
PubMed1984

Comparison of local versus central tumor measurements in a multicenter cancer trial.

Four hundred nineteen solid tumors from 92 patients were measured by a local team consisting of a physician and nurse oncologist or physician's assistant, and centrally by one radiologist. The central radiologist also remeasured 137 tumors on 30 patients to assess intraexaminer agreement. Tumor measurements at specific points in time as well as changes in tumor measurements over time were evaluated. When signed differences were calculated, there was little overall difference between local and central examiners, although three of the eight centers did show a significant difference. However, when absolute differences were calculated, the relative errors of the width times length products ranged from 35 to 55%. Although local and central examiners agreed 75% of the time on change in disease, there was only 42% agreement on the subset of patients who had a remission. In general, the intraexaminer agreement was slightly better than the interexaminer agreement. This study suggests that solid tumor measurements are not particularly reliable, and that survival time remains the most satisfactory endpoint in a cancer clinical trial.

Clinical Trials as Topic↗
PubMed1982

Platelets and malignancy. Rationale and experimental design for the VA Cooperative Study of RA-233 in the treatment of cancer.

Considerable evidence has accumulated in recent years which implicates blood coagulation reactions in the growth and spread of malignancy. In particular, platelets may accumulate on embolic tumor cells and facilitate their adhesion to the endothelium at distant sites perhaps by enhancing blood coagulation reactions. Alternatively, platelets may promote tumor cell proliferation by contributing a growth-promoting factor or through interactions mediated by prostaglandins. Inhibition of tumor growth and spread by platelet-inhibitory drugs has been demonstrated in several experimental tumor systems. Preliminary data suggest that similar effects may be seen in human malignancy. The purpose of this paper is to review relevant literature which provides the rationale for therapeutic trials of platelet-inhibitory drugs in human malignancy and to describe the experimental design for a trial involving one such drug, RA-233, in a recently established VA Cooperative Study.

Adenocarcinoma↗
PubMed1981

Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75.

In a controlled, randomized study, survival of patients with small cell carcinoma of the lung (SCCL) was prolonged on addition of warfarin sodium to combination chemotherapy plus radiation therapy. Median survival for 25 control patients was 24 weeks and for 25 warfarin-treated patients was 50 weeks. This difference could not be accounted for by differences between groups in performance status, extent of disease, age, or sex. The survival advantage associated with warfarin administration was observed both for patients with extensive disease and for those who failed to achieve complete or partial remission. The warfarin-treated group also demonstrated a significantly increased time to first evidence of disease progression. These results suggest that warfarin may be useful in the treatment of SCCL and also support the hypothesis that the blood coagulation mechanism may be involved in the growth and spread of cancer in man.

Antineoplastic Agents↗
PubMed1980

Remission of the Lambert-Eaton syndrome and small cell anaplastic carcinoma of the lung induced by chemotherapy and radiotherapy.

A patient presented with the Lambert-Eaton syndrome and small cell anaplastic carcinoma of the lung was subsequently diagnosed. Treatment with cytotoxic chemotherapy and radiotherapy resulted in remission of both the cancer and the neuromuscular disorder. This case represents the first documented remission of the Lambert-Eaton syndrome following nonoperative treatment of the primary malignancy and emphasizes the therapeutic value of early diagnosis of this disorder.

Antineoplastic Agents↗
PubMed1979

Rationale and experimental design for the VA Cooperative Study of Anticoagulation (Warfarin) in the Treatment of Cancer.

Anticoagulants have been demonstrated to reduce tumor growth in certain experimental animal systems. Inhibition of clot formation interferes with tumor growth and spread while enhancement of coagulation promotes tumor growth and spread. The fact that the coagulation mechanism is commonly activated in human malignancy together with preliminary reports of therapeutic efficacy of anticoagulants suggests that the coagulation mechanism may be of pathophysiologic significance also in the growth of human tumors. A VA Cooperative Study has been established to test the hypothesis that warfarin anticoagulation will modify the course of malignancy in man. The purpose of this paper is to present the rationale and experimental design for this study with emphasis on management of anticoagulant administration in cancer patients. This paper serves as the basis for forthcoming reports of toxicity and therapeutic efficacy of warfarin in human malignancy.

Animals↗
PubMed1978

Combination chemotherapy of non-Hodgkin lymphoma.

A randomized therapeutic trial of three induction regimens for patients with lymphosarcoma and reticulum-cell sarcoma was conducted by the Cancer and Leukemia Group B (CALGB) (formerly Acute Leukemia Group B.) Addition of streptonigrin, but not cyclophosphamide, to the combination of vincristine and prednisone improved the complete remission rate achieved after a 42-day induction program. The duration of the subsequent remission and survival was not influenced by the induction combination assigned. Remission maintenance with cyclophosphamide was superior to maintenance with methotrexate. The results of this study are compared with others in which advantages for three or four drug treatment regimens have been reported.

Antineoplastic Agents↗