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Biomedical subjects

D V Jackson

Publications and source records attributed to D V Jackson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Hepatic intra-arterial infusion of vincristine.

Currently the chemotherapeutic agents available for intra-arterial infusion in metastatic liver cancer are limited to only a few. The recent demonstration of the feasibility of prolonged IV infusion of vincristine led to exploration of hepatic intra-arterial infusion of this agent. A continuous infusion of 0.4 mg total dose was administered daily for 5 days via a hepatic artery catheter to each of six patients with metastatic liver cancer. Transient but life-threatening toxicity principally involving the nervous and gastrointestinal systems occurred in five of them. Future investigation of hepatic intra-arterial infusion of vincristine should be based on dose-schedules other than that employed in the current trial.

Adult↗
PubMed1984

Synergistic antitumor activity of vincristine and VP-16-213.

The potential interaction of the antitumor agents vincristine and VP-16-213 was investigated in vivo. DBA/2 mice were inoculated with 10(6) P388 murine leukemia cells, after which single IP injections of saline only, vincristine only, VP-16-213 only, or a combination of vincristine and VP-16-213 were administered. Long-term survival (greater than 60 days) was observed in 0/45, 1/45 (2%), 9/135 (7%), and 44/135 (33%) mice, respectively (P less than 0.001). Treatment was most effective when VP-16-213 was administered 0-72 h after vincristine. A similar trend was observed in mice bearing P1534 murine leukemia. These data demonstrate synergistic antitumor activity between vincristine and VP-16-213 in a murine model.

Animals↗
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

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

Prospective evaluation of changes in computed cranial tomography in patients with small cell lung carcinoma treated with chemotherapy and prophylactic cranial irradiation.

Computed cranial tomographic scans were performed as part of the pretreatment evaluation and at six- to nine-month intervals posttreatment in 13 patients with small cell lung carcinoma. All patients received 3,000 rad of prophylactic cranial irradiation delivered over two weeks in ten treatment fractions in conjunction with multiagent chemotherapy. Posttreatment scans documented an extraordinarily high frequency of abnormalities including cerebral atrophy (100%), ventricular dilatation (70%), and decreased coefficient of absorption in the white matter (15%). Unexplained neurologic abnormalities developed in four of six patients living at least 15 months after institution of therapy. As the number of long-term survivors of this type of lung cancer increases, the need for prospective comprehensive neuropsychologic assessment to determine the clinical significance of these changes is needed.

Aged↗
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

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

Glutamic acid modification of vincristine toxicity.

The principal limiting feature of the antitumor agent, vincristine, in the clinic has been neurotoxicity; there are no known agents which can routinely prevent or decrease this side effect. Glutamic acid in laboratory and clinical investigations in the early 1960s was found to antagonize vinblastine, another clinically useful vinca alkaloid. Glutamic acid 250 mg/kg/d i.p. was given to normal mice treated with repetitive doses of vincristine 1.5 mg/kg every other day. When glutamic acid was given both before and during vincristine administration, it produced a 49-79% increase in survival compared to control mice receiving vincristine only (p less than 0.01). Other schedules of glutamic acid administration were ineffective. Also, there appeared to be a delay in development of neurotoxic manifestations (toe-walking gait) but the results were not as consistent as the improvement in survival. Glutamic acid given to tumor-bearing mice (P-388 and P-1534 murine leukemia) did not inhibit the antitumor effect of vincristine-induced host toxicity in a schedule-dependent fashion without inhibition of the antitumor effect of vincristine.

Animals↗
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

Vincristine, doxorubicin and mitomycin (VAM) in patients with advanced breast cancer previously treated with cyclophosphamide, methotrexate and fluorouracil (CMF). A clinical trial of the Piedmont Oncology Association (POA).

Thirty-six evaluable patients with advanced breast cancer who had failed prior CMF therapy [15 (42%) as adjuvant treatment and 21 (58%) for advanced disease] were treated with a combination of vincristine, doxorubicin, and mitomycin (VAM). There was one CR and 10 PR, giving a response rate of 31% (P, 95% confidence interval, 15%-47%). Response was not significantly related to age, performance status, disease-free interval, dominant site of disease, number of sites of disease, or estrogen receptor status. The median duration of response was 5 months for patients attaining CR or PR and 4.6 months for patients with stable disease. The median survival for patients with CR or PR of 7.9 months was not better than for those with stable disease (8.0 months), but both groups had significantly longer survival than those with initial progression. Patients who received VAM after failing adjuvant CMF had a 53% response rate (8 of 15), as against a 14% response rate (3 of 21) in those failing CMF for advanced disease (P less than 0.05). In spite of this difference, the survival distributions for these two groups were not significantly different. Myelosuppression was moderate and no cardiac toxicity was seen. The addition of mitomycin to vincristine and doxorubicin in previously treated patients does not appear to improve the results obtained with vincristine and doxorubicin alone.

Adult↗
PubMed1983

Continuous intravenous infusion of vinca alkaloid using a subcutaneously implanted pump in a canine model.

A major drawback of infusions of the vinca alkaloids is the lengthy period of hospitalization which is often required for this novel technique of cancer therapy. A potentially useful system to deliver outpatient therapy has been investigated in a preclinical study. A self-contained infusion pump powered by a self-charging fluorocarbon system has been implanted SC in three dogs. The performance of two pumps which had been factory-calibrated to deliver 2.5 and 4.5 ml/day, respectively, was evaluated during 22 infusions of the vinca alkaloids (vincristine, 7; vinblastine, 7; and vindesine, 8). Infusions were given over a 5- to 7-day period and were repeated at 3-week intervals. No malfunctioning of the pumps occurred in over 500 cumulative days of use. The flow rates of the pumps were quite stable except in one animal whose increased flow rate was probably a consequence of fever due to self-induced inflammation about the pump pocket. No local or distant tissue reactions to the pump were observed. Decomposition of vincristine and vinblastine in the infusate at the end of 5- or 7-day infusions was minimal as determined by high-pressure liquid chromatography. The amount of decomposition of vindesine in the infusate was variable. Steady-state concentrations of vincristine during infusion were always greater than 10(-9) M, and were similar to those previously determined in our clinical infusion trials using a dosage of 0.5 mg/m2/day. Clinical evaluation of this system for prolonged infusions of vincristine and other vinca alkaloids appears to be warranted.

Animals↗
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

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↗