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Biomedical subjects

F Richards

Publications and source records attributed to F Richards.

At least 109 records · Page 6Linked to original sources
PubMed1984

Leukemogenesis related to chemotherapy of ovarian carcinoma: a review with three new case reports.

A review of the literature of 68 case reports of acute leukemia following ovarian cancer is presented and 3 new cases are reported. Review of the literature revealed 34 patients received chemotherapy and radiotherapy, 32 patients received chemotherapy alone, 1 patient had only surgery, and the radiation status of the remaining patient is unclear. Chemotherapy usually consisted of alkylating agents often given in high dose and for long durations. The reported risk for developing acute leukemia after treatment of ovarian cancer ranges from 21 to 175 times that of the general population with a prevalence range in treated patients of 0.8 to 2.7%. The median interval from initiation of therapy to the development of leukemia is shortened from 54.2 to 41.1 months if radiation therapy is used in addition to chemotherapy. The patients typically exhibit a brief preleukemic phase and poor survival with death occurring 3 to 5 months after diagnosis of leukemia. Proposed mechanisms for leukemogenesis are presented.

Antineoplastic Agents↗
PubMed1984

Bone marrow evaluation in small cell lung cancer.

The records of 87 patients with small cell lung cancer were reviewed. Patients were clinically staged with bone marrow aspirate and biopsy as well as radionuclide scans of bone, liver, and brain. Extrathoracic spread was noted in 54% (47/87) and limited disease in 46% (40/87). The bone marrow evaluation was positive in 13/62 patients (21%) and seven of these thirteen patients had normal bone scans (54%). Of these seven patients, five had no other evidence of distant metastases and their survival was 7-10 months, considerably shorter than patients found to have limited disease. Bone marrow examination appears to complement radionuclide scanning in the initial staging of patients with small cell carcinoma of the lung and provides important prognostic information.

Bone Marrow Examination↗
PubMed1984

The treatment of melanoma with m-AMSA. A Cancer and Leukemia Group B phase II study.

The activity of m-AMSA was evaluated IN 39 patients with advanced malignant melanoma. Seventy-nine percent of the patients had some prior chemotherapy. The others had some combination of surgery, radiotherapy, and immunotherapy prior to this study. Patients were treated every 3 weeks starting with 60 or 120 mg/m2 of m-AMSA depending on the extent of prior treatment. Doses were escalated if nadir WBC counts were greater than 2500/microliter. Leukopenia was the dose-limiting toxicity with 7.5% of patients having nadir WBC counts less than 1000/microliter. Of the 39 patients evaluable for response, all had progressive disease. In this study, m-AMSA in myelosuppressive doses was not active in malignant melanoma.

Adult↗
PubMed1984

A phase II study of dibromodulcitol (DBD) in stage IV melanoma.

Twenty-four patients were evaluated in a non-randomized study to assess the effectiveness of dibromodulcitol (DBD) in Stage IV melanoma. Patients received 100 mg/m2 of DBD orally for 35 days. The dose was escalated to 130 mg/m2 and then to 160 mg/m2 if no significant hematologic toxicity occurred. There were no objective responses, including six patients who had had no prior chemotherapy. Five patients (21%) remained stable. Median survival was 151 days. Survival favored females, nonvisceral involvement pretherapy, and patients with a disease-free interval (DFI) of greater than 1 year. None of these advantages was statistically significant. Toxicity was predominantly hematologic, but nausea, vomiting, shortness of breath, and diarrhea were also seen. Oral DBD, using this dose and schedule, does not appear efficacious in advanced disseminated melanoma.

Drug Administration Schedule↗
PubMed1984

VP-16-213 in combination chemotherapy with chest irradiation for small-cell lung cancer: a randomized trial of the Piedmont Oncology Association.

The role of etoposide epipodophyllotoxin (VP-16-213) in a combined modality treatment program incorporating local chest irradiation and combination chemotherapy with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine has been evaluated in a randomized trial of 165 patients with small-cell lung cancer. The overall response rate (complete response [CR] plus partial response [PR]) was significantly greater in the VP-16-213 arm (85% v 64%, P = .005) primarily as a consequence of improved response in patients with extensive disease (85% v 38%, P = .002 and 30% v 8% for CR only, P = .045). No differences in the response rates were observed in limited disease. The duration of response (months) was greater in the VP-16-213 arm (8.6 v 7.0 overall and 14.4 v 11.5 for CR) but not significantly so. Median survival times (months) were consistently greater in the group receiving VP-16-213 when analyzed according to extent of disease and response (10.6 v 9.5 overall; 15.0 v 13.6 for limited disease; 9.0 v 6.7 for extensive disease; 18.5 v 16.2 for CR overall; and 18.6 v 16.1 for CR in limited disease); the results were not statistically significant. The median survival of extensive disease patients attaining a CR was 15.3 months (range 3.2 to 34.3 + months) in the VP-16-213 arm and 7.4+ and 8.1+ months for the two patients with CR in the other group. Anemia and leukopenia occurred to a greater degree in the four-drug regimen, but no unusual or significant compounding toxicity (ie, neurotoxicity) was observed otherwise. Further investigation of this agent in combination chemotherapy programs for small-cell lung cancer appears to be warranted.

Adult↗
PubMed1984

The effects of prior radiation therapy and age on the frequency and duration of complete remission among various four-drug treatments for advanced Hodgkin's disease.

The current report examines the clinical response observed in 137 patients with advanced Hodgkin's disease who had relapsed from an initial complete response following radiation therapy (RTF) in comparison to 280 patients with no prior therapy (NPT). Patients were prospectively randomized to therapy with a four-drug combination chemotherapy program to determine whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine when combined with procarbazine and prednisone. The frequency of complete remission (CR) was 75% for the RTF group compared to 60% of those with NPT (P = .005). In the RTF group, those patients receiving a nitrosourea (CCNU) had a significantly greater CR frequency than those receiving mechlorethamine (P = .006). Significant risk factors favoring longer duration of remission were age less than 40 (P = .005), the absence of splenic involvement (P = .007), and the use of CCNU-containing programs (P = .015). The advantage for CCNU-containing programs was seen only in patients less than 40 years of age. In this study, the strongest factors favorably affecting response to therapy were prior RTF, age less than 40 years, and treatment with a nitrosourea (CCNU).

Adult↗
PubMed1984

A phase II study of recombinant alpha interferon in patients with recurrent or metastatic breast cancer.

Thirty-three patients with advanced breast cancer were treated with a recombinant alpha interferon (rIFN-alpha 2). All patients were ambulatory (performance status greater than or equal to 50 Karnofsky scale) and almost all had received previous chemotherapy. Large intravenous dosages of 30 to 50 X 10(6) IU/m2 were given for five consecutive days every two to three weeks to 22 patients and smaller subcutaneous dosage of 2 X 10(6) IU/m2 three times a week to 11 patients. No complete or partial responses were seen. Two patients had stable disease and the remainder progressed. Flu-like syndromes were seen in all patients. Nausea, vomiting, and anorexia were frequent. Hypotension and confusion were noted in six and five patients, respectively. Life-threatening leukopenia was noted in two patients receiving intravenous dosage and thrombocytopenia was noted in one; no sepsis or bleeding complications were noted. In this study, a highly purified and biologically active rIFN-alpha 2 was not associated with activity in previously treated women with metastatic breast cancer.

Adult↗
PubMed1984

Treatment of poor risk acute leukemia with sequential high-dose ARA-C and asparaginase.

Resistance of leukemia cells to cytosine arabinoside (ARA-C) may be due to any one or combination of biochemical processes, which in certain instances may be substantially reversed by an appropriate increase in ARA-C dosage. Based on these and other laboratory observations indicating pharmacologic synergy between sequential high-dose ARA-C and asparaginase (HiDAC----ASNase), a therapeutic program was developed for the treatment of patients with acute nonlymphocytic leukemia (ANLL) refractory to conventional doses of ARA-C, as well as patients with high risk ANLL and advanced acute lymphocytic leukemia (ALL). Treatment consisted of 3-hr intravenous infusions of 3 g/sq m of ARA-C given at 12-hr intervals for 4 doses, followed by 6,000 IU/sq m ASNase given i.m. at hour 42. The same schedule was repeated on day 8. In 32 induction attempts, only 4 patients proved to be truly refractory, i.e., failed to achieve substantial leukemia cell cytoreduction. Complete remissions were achieved with HiDAC---- ASNase in 9 of 13 patients with refractory ANLL, 6 of 9 patients with antecedent hematologic disorders, and 3 of 10 patients with advanced ALL. These include 9 of 14 patients who had either failed induction or who had relapsed on active ARA-C therapy and 6 of 8 patients who had had no prior exposure to ARA-C. The median duration of unmaintained remission in ANLL was 5 mo. In a patient with central nervous system (CNS) leukemia, there was clearance of cerebral spinal fluid (CSF) blasts without intrathecal therapy, suggesting a role for HiDAC in CNS prophylaxis. In general, toxicity was tolerable and reversible. These data suggest that HiDAC----ASNase is an exceptionally effective and well tolerated regimen in leukemic patients with antecedent hematologic disorders and in those refractory to conventional doses of ARA-C.

Acute Disease↗
PubMed1984

Informed consent: patient information forms in chemotherapy trials.

Documentation of informed consent by patients entering clinical trials is an ethical and legal necessity. Federal regulations and judicial opinions have led to increasingly lengthy, detailed "consent" forms, yet published studies demonstrate that patients remain confused about the nature and anticipated consequences of study entry. It has been suggested that more detail may even alarm or further confuse patients. Seventy-five women undergoing chemotherapy for advanced breast cancer participated in this study which assessed patient preference for long-, medium-, or short-form length, and whether form length preference correlated with patient characteristics or indicators of patient autonomy in decision-making or physician dependency. Patient preferences for information were not predicted by the patient autonomy or physician dependency scores or by age, marital status, or level of education. The majority of patients expressed a preference for more detailed information about their treatment, yet a majority of patients given detailed forms answered questions basic to the study design incorrectly, irrespective of educational level. The increased detail included in the long forms was not reported to increase stress compared to the short forms. Patient information forms are a principal tool for informing patients for consent but if they are to perform their desired function they must be designed more carefully and evaluated more thoroughly than in the past.

Age Factors↗
PubMed1983

CCNU in combination chemotherapy for advanced histologically unfavorable non-Hodgkin's lymphoma.

During a 3-year period 39 evaluable patients with stage III and IV non-Hodgkin's lymphomas and unfavorable histologies were treated with a unique chemotherapeutic regimen based on a modified CHOP combination to which was added the nitrosourea, CCNU. Complete response was observed in six of 15 (40%) patients with diffuse poorly differentiated lymphocytic lymphoma (DPDL), four of 11 (36%) with diffuse mixed histiocytic lymphocytic (DML), and seven of 13 (54%) with diffuse histiocytic lymphoma (DHL). Of the 17 patients who achieved complete response, nine (53%) have remained continuously disease-free for greater than 2.5 years (2.7-4.1 years) from the onset of therapy: four of six with DPDL, two of four with DML, and three of seven with DHL. Median survival was 18.9 months for all patients, 18.9 months for those with DPDL, 17.4 months for those with DML, and 9.7 months for those with DHL. The median survival has not been reached for patients who attained a complete response, and will exceed 3.3 years. Central nervous system relapse was observed in three patients. In general, toxicity was moderate and consisted primarily of leukopenia, nausea, vomiting, and neurotoxicity. There were no drug-related deaths. The addition of CCNU to a modified CHOP combination resulted in an effective, generally well-tolerated out-patient regimen. However, it did not appear to decrease the rate of CNS relapse or improve current treatment results observed with other adriamycin-containing regimens for similar patients.

Adolescent↗
PubMed1983

Lack of potentiation of vincristine-induced neurotoxicity by VP-16-213.

Due to a recent alarming report suggesting that the severe neurotoxicity observed following treatment with a multiagent chemotherapy regimen might be due to the interaction of vincristine and VP-16-213, the neurologic toxicity data from a randomized trial conducted by the Bowman Gray School of Medicine and the Piedmont Oncology Association in small cell carcinoma of the lung have been analyzed. Of 102 patients evaluable for toxicity, 50 were treated with a combination of cyclophosphamide, adriamycin, and vincristine (CAV) and 52 received this regimen plus VP-16-213. Vincristine dosage was the same in both arms of the study. When analyzed by severity, neurologic complications were similar in both treatment groups: Grade 1-2 neurotoxicity occurred in 55% of patients on both arms and grade 3-4 neurotoxicity was observed in six (12%) patients on the CAV arm and four (8%) on the CAV-VP-16-213 arm. Addition of VP-16-213 to vincristine did not potentiate vincristine-induced neurotoxicity when administered in this dose-schedule relationship.

Adult↗
PubMed1983

Bleomycin-induced cutaneous toxicity in the rat: analysis of histopathology and ultrastructure compared with progressive systemic sclerosis (scleroderma).

Rats injected with bleomycin over a 58-week period developed weight loss, alopecia, hyperpigmentation, skin thickening and skin tautness when compared with saline-injected control animals. The only significant abnormality in laboratory blood tests was an increased sedimentation rate in the bleomycin-treated rats compared with controls. Histological examination of dorsal skin showed atrophied sebaceous glands and increased collagen fibres, with diameters ranging from 37.5 to 75 nm as compared with 72.5 to 100 nm in control animals. Chronic bleomycin exposure produces clinical, histological and ultrastructural skin changes similar to those found in human progressive systemic sclerosis (scleroderma).

Animals↗
PubMed1983

Vincristine by continuous infusion in refractory breast cancer: a phase II study.

Eighteen patients with advanced refractory breast carcinoma were treated with vincristine (VCR), 0.5 mg I.V. bolus followed by continuous I.V. infusions of 0.25 mg/m2/day for 5 days every 3 weeks. The daily dose of VCR was infused in 1000 ml D5W to which was added hydrocortisone 50 mg and heparin 3000 U. Patients received from one to six courses (mean 2.3 courses). No objective responses were observed. Stable disease was noted in five patients who had skeletal metastases only. Disease progression occurred in the remaining 13 patients, 10 of whom had received prior VCR by bolus injection. The principal toxicity consisted of constipation without ileus and hyporeflexia-paresthesias. Vincristine, administered by continuous I.V. infusion according to this dose and schedule does not appear to be effective in the treatment of patients with advanced refractory breast cancer.

Breast Neoplasms↗
PubMed1982

Vincristine, doxorubicin, and cyclophosphamide versus low-dose intravenous cyclophosphamide, methotrexate, and 5-fluorouracil in advanced breast cancer: a randomized trial of the Piedmont Oncology Association.

Eighty-one evaluable patients with recurrent or metastatic breast cancer were randomized to receive either vincristine 1 mg/m2, doxorubicin 40 mg/m2 on day one and cyclophosphamide 200 mg/m2 orally days 3-6 (VAC); or cyclophosphamide 350 mg/m2, methotrexate 20 mg/m2, and 5-fluorouracil 350 mg/m2 (CMF) intravenously, all on day 1. Courses of each of the above regimens were repeated every three weeks. Twenty-one of 45 patients (47%) on VAC and seven of 44 patients (16%) on CMF had complete or partial response (P less than 0.05). The duration of response was six months for CMF and nine months for VAC. Hematologic toxicity was minimal for both groups but three patients receiving VAC developed cardiac toxicity. Overall survival projections at this time indicate no differences between the VAC or CMF treated patients.

Antineoplastic Agents↗