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Biomedical subjects

D V Jackson

Publications and source records attributed to D V Jackson.

At least 91 records · Page 5Linked to original sources
PubMed1982

Nonseminomatous germ cell cancer of the testis. Reducing treatment-related morbidity in patients with disseminated disease.

Fourteen previously untreated patients with metastatic nonseminomatous germ cell cancer of the testis (NSGC) were treated with a modified VAB-4 regimen which was designed to reduce treatment-related morbidity. Nine of 10 patients with minimal disease and the only patient with advanced pulmonary disease achieved a complete response (CR) with chemotherapy alone. Two of three partial responders with advanced abdominal disease were converted to CR status with radiotherapy and/or surgery. None of the 12 CRs have relapsed (median duration of follow-up, 28+ months). We observed no granulocytopenic fever or permanent renal insufficiency. These results indicate that NSGC patients with a low tumor burden can be spared substantial toxicity without adversely affecting complete response rates.

Antineoplastic Agents↗
PubMed1982

Nonseminomatous germ-cell cancer of the testis.

Fourteen previously untreated patients with metastatic nonseminomatous germ-cell cancer of the testis (NSGC) were treated with a modified VAB-4 regimens that was designed to reduce treatment-related morbidity. Nine of ten patients with minimal disease and the only patient with advanced pulmonary disease achieved a complete response (CR) with chemotherapy alone. Two of three partial responders with advanced abdominal disease were converted to CR status with radiotherapy and/or surgery. None of the 12 CRs has had a relapse (median duration of follow-up, 28+ months). We observed no granulocytopenic fever or permanent renal insufficiency. These results indicate that NSGC patients with a low tumor burden can be spared substantial toxicity without the complete response rates being adversely affected.

Antineoplastic Agents↗
PubMed1982

Combination chemotherapy-radiotherapy with and without the methanol-extraction residue of Bacillus Calmette-Guerin (MER) in small cell carcinoma of the lung: a prospective randomized trial of the Piedmont Oncology Association.

The effect of addition of the nonspecific immunostimulant, MER, to combined treatment with chemotherapy and radiotherapy in small cell carcinoma of the lung was evaluated in a prospective randomized trial involving 102 evaluable patients. Chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, methotrexate, and CCNU; and radiotherapy was administered to the primary lesion, mediastinum, supraclavicular areas, and whole brain. Of 47 patients administered MER 400 mcg intradermally every six weeks, 12 (26%) attained complete remission with a median survival of 22.9 months. Complete remission was observed in 17 (31%) of 55 patients who received no MER with a median survival of 20.0 months (P greater than 0.05). Survival greater than or equal to 2 years has been observed in five patients who received MER and two patients who did not receive MER. The response rate and duration, survival, and toxicity of the two treatment arms were similar with the exception of cutaneous and occasional systemic reaction to MER. MER as used in this study has not influenced the overall results of a combined modality treatment program for patients with small cell carcinoma of the lung.

Adult↗
PubMed1982

Treatment of vincristine-induced ileus with sincalide, a cholecystokinin analog.

Sincalide, a synthetic analog of cholecystokinin capable of stimulating bowel motility, has been administered to 12 patients with symptoms and signs of vincristine-induced ileus. Patients were given intravenous infusions of sincalide 0.01 microgram/kg/h over 2-24 h (mean, 8 h) for 1-12 days (mean, 5 days), usually until all evidence of ileus had resolved. Improvement was noted within 48 h of initiation of therapy in eight patients (75%), whereas marginal or no responses were observed in four patients. The mean duration of ileus was 3.6 days in responders and 7.7 days in nonresponders. Toxicity was minimal and consisted of diarrhea in two patients, in whom symptoms promptly resolved with discontinuation of the drug. Further explorations of this promising agent in the treatment of vincristine-induced ileus appears warranted.

Cholecystokinin↗
PubMed1981

Intravenous vincristine infusion: phase I trial.

In an attempt to sustain potentially cytotoxic concentrations of vincristine in man, a five-day continuous infusion of vincristine after an initial intravenous bolus injection was administered to 30 patients with refractory malignancies. Three dosage levels were explored (0.5 mg/m2, 0.75 mg/m2, and 1.0 mg/m2 daily for five days). Neurologic and hematologic toxicity were severe at the high dose level, whereas mild to moderate toxicity occurred at the 0.5 and 0.75 mg/m2 dose levels. Objective responses were noted in 11 patients (37%) with the following malignancies: non-Hodgkin's lymphoma (4), acute non-lymphoblastic leukemia (2), chronic granulocytic leukemia in blast crisis (1), carcinoma of the breast (3), and small cell carcinoma of the lung (1). Responses were observed at each infusion dose level. Nine of the 11 responders had previously progressed while receiving conventional intravenous bolus injection of vincristine. These data suggest that the clinical usefulness of vincristine may be enhanced by the use of infusion techniques. A maximum daily dose of 0.5 mg/m2 given for five days is recommended for future trials of intravenous vincristine infusion.

Aged↗
PubMed1981

Combination chemotherapy with and without the methanol-extracted residue of bacillus Calmette-Guerin (MER) in extensive non-small-cell lung cancer: a prospective randomized study for the Piedmont Oncology Association.

One-hundred-three patients with extensive non-small-cell lung cancer were entered into a prospective, randomized trial to determine the value of MER as an adjuvant to chemotherapy. Patients were stratified according to histology and performance status. All patients received CCNU, methotrexate, and Adriamycin with 48 patients also receiving MER. All patients had a performance status of 2 or less (less than 50% bedridden), 49% had prior radiation therapy, only one patient had prior chemotherapy, and all had extensive disease. Of the patients, 42% had epidermoid cancer, 21% had large cell cancer, 32% had adenocarcinoma, and 4% had mixed adenosquamous or undifferentiated carcinoma. The response rates and response durations of the two treatment regimens were similar. Of the patients, 18% had an objective response; in 4% it was complete. An additional 29% had a stable response. Median duration of response ranged from 21 to 23 weeks. Median survival rates for non-MER and MER treatment groups were 21.5 and 18.6 weeks, respectively. The four complete responders have a survival of 24, 85, 86+, and 129 weeks. MER did not improve response for hematopoietic tolerance, was associated with significant morbidity, and was poorly tolerated. The value of immunotherapy in lung cancer remains to be established.

Adenocarcinoma↗
PubMed1981

A randomized comparative trial of chemotherapy and irradiation therapy for stage II breast cancer.

One hundred fifty-eight evaluable patients with Stage II carcinoma of the breast with positive lymph nodes were treated either with adjuvant chemotherapy or irradiation therapy followed by chemotherapy. Patients were randomized to test the effectiveness of L-phenylalanine mustard (L-PAM) with and without postoperative irradiation therapy (R.T.) against cyclophosphamide, 5-fluorouracil, and methotrexate (CMF) with and without postoperative irradiation therapy in decreasing the frequency of recurrence. No significant difference was observed between L-PAM as compared with R.T. plus L-PAM (P = 0.85). The difference between CMF and R.T. plus CMF was significant in support of CMF alone (P = 0.04). The frequency of recurrence between R.T. plus L-PAM and R.T. plus CMF showed no difference. A comparison of the chemotherapy only regimens showed an advantage of CMF over L-PAM (P = 0.05). Both the delay in starting chemotherapy and the significant decrease in percent optimal drug dosage during the first six cycles of therapy are factors that may influence the high frequency of relapse observed in the R.T. plus chemotherapy groups. Of the four treatments, CMF has the lowest frequency of recurrence.

Adult↗
PubMed1981

Chemotherapy vs. chemoimmunotherapy with methanol extraction residue of Bacillus Calmette-Guerin (MER) in advanced breast cancer: a randomized trial by the Piedmont Oncology Association.

Effects of the addition of MER, a nonspecific, nonviable immunostimulant, to two combination chemotherapy programs were explored in patients with metastatic breast cancer. Patients were randomized to either CDVFP [cyclophosphamide (C), doxorubicin (D), vincristine (V), fluorouracil (F) and prednisone (P)] or CD alternating with methotrexate (M) and F (CD/MF). Each group was also randomized to receive MER, 0.4 mg S.C. every four weeks or no immunotherapy. The response rates were CDVFP 56%, CDVFP + MER 54%, CD/MF 43%, and CD/MF + MER 43%. No significant differences were noted in response rate. Median durations of response and survival were similar for each group: CDVFP 16.2 and 25.2 months, respectively; CDVFP + MER 14.0 and 23.3 months, CD/MF 12.1 and 26.1 months, and CD/MF + MER 15.5 and 25.6 months. Patients who achieved CR frequently had soft-tissue disease (7/17) and patients with disease in 1 or 2 metastatic sites had a significantly higher response rate than those in greater than or equal to 3 sites. MER did not enhance response rate, duration of response, or survival. Also MER did not diminish myelosuppression.

Antineoplastic Agents↗
PubMed1981

Cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil in advanced prostatic cancer: a randomized trial.

Thirty-two evaluable patients with metastatic carcinoma of the prostate were entered into a prospective randomized trial comparing cyclophosphamide (CYC) with a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF). Progressive disease after endocrine manipulation was noted in 97% (31/32) of patients before entry. Stable disease (S) was observed in 9 of 17 patients treated with CYC. One partial response (PR) and seven stable responses occurred in the 15 CMF patients. Median duration of stable response was 4.5 months for CYC and 4.5 months on CMF. Median survival of patients with PR and S receiving CYC was 10.1 and for CMF 8.8 months. Patients with progressive disease survived a median 1.7 and 2.6 months with CYC and CMF, respectively. Toxicity was moderate, and no deaths were attributable to sepsis or bleeding. Almost all patients in this study had bone lesions as the dominant site of disease; this made objective assessment of response difficult. There was no significant improvement in response conferred by the combination regimen. Although patients with metastatic prostatic cancer may benefit from chemotherapy, impressive clinical responses are uncommon.

Aged↗
PubMed1981

Unusual immunofluorescence patterns for terminal deoxynucleotidyl transferase in blast crisis chronic myelogenous leukemia.

An unusual cytoplasmic distribution of terminal deoxynucleotidyl transferase (TdT) antigen in leukemic cells from two patients who had chronic myelogenous leukemia in blastic phase is described. In most leukemic cells that contain TdT, the intracellular location has been reported to be exclusively nuclear. The cells from these two patients demonstrated TdT staining in both the nucleus and the cytoplasm. The pattern is remarkably similar to that observed in thymocytes, in which bright cytoplasmic staining may also be seen. In the immunofluorescence procedures for detection of TdT in blasts from patients who have chronic myelogenous leukemia, significant cytoplasmic staining should not be mistaken for nonspecific absorption of immunoglobulins or specimen deterioration.

Adult↗
PubMed1981

Pharmacokinetics of vincristine in the cerebrospinal fluid of humans.

Using a sensitive radioimmunoassay, concentrations of vincristine and its products were determined in cerebrospinal fluid (CSF) and corresponding blood samples from four patients with lymphoma and two patients with leukemia who had received i.v. bolus injection of 2 mg vincristine. Serial samples of CSF were withdrawn from a CSF reservoir in two patients during a 24-hr period following injection. The first time point after injection at which measurable levels of vincristine were detected in the CSF was 30 min; the concentrations were within the lower range of sensitivity of the assay and were 20- to 30-fold lower than were corresponding serum samples. Despite a prolonged terminal half-life of vincristine in the serum (14.4 to 37.5 hr) following i.v. bolus injection, concentrations of vincristine in the CSF ranged between undetectable within the limits of the assay and 1.1 X 10(-9) M during the 24-hr period of observation. The highest CSF concentration of vincristine (2.6 X 10(-9) M) has been observed in a patient receiving cranial irradiation for active meningeal lymphoma. No measurable levels of vincristine or its products were detected in spot samples of CSF from three patients. Penetration of vincristine and its products into the CSF of humans after i.v. bolus injection appears to be very poor and may account for the uncommon occurrence of central neurotoxicity following its clinical use.

Adolescent↗
PubMed1981

Pharmacokinetics of vincristine sulfate in adult cancer patients.

Vincristine concentration in serum from 1 min to 72 hr was measured by radioimmunoassay in 14 patients with cancers following i.v. bolus injection of vincristine sulfate at 0.45 to 1.30 mg/sq m. The pharmacokinetic data were analyzed by a nonlinear least-square regression program NONLIN. A three-compartmental open model fitted the raw data better than a two-compartmental model. The mean half-lives of the triphasic decay curves alpha, beta, and gamma were 1.9, 19.2, and 1359 min (22.6 hr), respectively. The apparent volume of the central compartment and the volume of distribution at steady state (Vdss) per 1.73 sq m body surface area were 4.1 and 167.6 liters, respectively. The plasma clearance was 141.9 ml/min/1.73 sq m, and the area under the concentration X time curve from 0 to infinity (AUC0 infinity) for 2 mg vincristine was 21,689 nM.min. Linear regression analysis of the data gave evidence for increasing plasma clearance at higher doses of vincristine. In patients with higher platelet counts, lower AUC0 infinity values were obtained, suggesting a possible interaction of vincristine with blood platelets. Our results, a large Vdss, a long biological half-life, and a low rate-limiting rate constant from Compartment 3 to the central compartment (k31), indicate an avid tissue binding and a slow drug release from the body tissues which may account for drug-related neurotoxicity.

Adult↗
PubMed1980

Advanced epidermoid lung cancer: prolonged survival after chemotherapy.

The charts and pathologic reports for 4 patients seen at our institution with advanced incurable epidermoid carcinoma of the lung, who had prolonged disease-free survival after chemotherapy, were reviewed. All patients had Stage III bronchogenic carcinoma. Our study indicates that patients with epidermoid carcinoma of the lung who achieve a complete response have a better survival than those patients who have a partial response or no response. All complete responses were achieved after two to three months of chemotherapy, and if a response is not seen by then a modification of the treatment program is recommended. We propose that complete response should be considered the most important prognostic factor for therapeutic trials in epidermoid carcinoma of the lung.

Antineoplastic Agents↗
PubMed1980

A sensitive radioimmunoassay for vincristine and vinblastine.

A rapid, sensitive and highly reproducible radioimmunoassay (RIA) has been devised for vincristine and vinblastine. These alkaloids bind to the antiserum very tightly with an association constant (Ka) of 5 x 10(9) M-1 as determined by Scatchard analysis. The kinetic association constant of the alkaloids, as determined by the 'on' and 'off' rates at 4 degrees C, is 30-fold higher than the Scatchard analysis value. At 4 degrees C, 80% of the alkaloid is bound to the antiserum within 20 min, and the remaining 20% reaches an equilibrium within 48-72 h. In the RIA procedure the amount of the alkaloid (1-2 ng) needed to compete for 50% binding remains unchanged when the reaction mixtures are incubated for 2, 4, or 20 h. By a modification of the RIA procedure, where the antiserum is first allowed to react with the unlabeled alkaloid followed by addition of the radiolabeled alkaloid, sensitivity of the assay has been increased five- to tenfold. Other drugs, such as adriamycin, CCNU, methyl CCNU, cyclophosphamide, 5-fluorouracil, heparin, hydrocortisone, prednisone, and nitrogen mustard do not interfere with the assay. This assay can thus be used to determine vincristine or vinblastine levels in 5 x 10(-10)--10(-9) M concentrations in biological fluids.

Antibodies↗
PubMed1980

Actinomycin D in the treatment of advanced breast cancer.

Actinomycin D is generally administered by serial low-dose injection over 5-10 days. Recent recognition of prolonged serum and tissue half-lives suggests that high-dose intermittent injecton should be equally effective and less toxic. An intermitten single dose schedule was selected for this phase II trial of actinomycin D in 23 patients with advanced breast cancer refractory to standard combination chemotherapy. The drug was given in doses of 0.75-1.5 mg/m2 at 2-week intervals or on days 1 and 8 of 28-day treatment cycles. One patient obtained a partial response with a duration of 5.7 months. Four patients experienced stabilization of advanced disease, with a mean duration of response of 6.4 months. Gastrointestinal toxicity occurred in 47% of patients and mild to moderate myelosuppression in 39%. We conclude that actinomycin D in this dosage and schedule has limited activity in advanced breast cancer. Higher doses might result in increased response rates but would be associated with greater toxicity.

Breast Neoplasms↗
PubMed1980

Interaction of albumin and vincristine with a human lymphoblastic leukemia cell line in vitro.

To investigate the potential influence of albumin on the antitumor effect of vincristine (VCR), cells from a human lymphoblastic leukemia cell line (CEM) were exposed in vitro to albumin and a clinically attainable VCR concentration (10(-7)M). Increasing concentrations of albumin between 1 and 4 g/100 ml resulted in a corresponding reduction of VCR-induced growth suppression. Studies employing tritiated vincristine ([3H]-VCR) revealed a progressive inhibition of uptake of the radio-label into CEM cells with increasing concentrations of albumin. These in vitro data show a previously unrecognized protective effect of increasing concentrations of albumin on the growth of human lymphoblastic leukemia cells exposed to VCR as a consequence of inhibition of drug uptake. Further in vivo pharmacologic studies will be necessary to determine their clinical significance.

Biological Transport↗