Changing trends in small cell lung cancer.
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Adult↗
Biomedical subjects
D V Jackson
Publications and source records attributed to D V Jackson.
Small-cell lung cancer: a 10-year perspective.
Over the past 10 years, four clinical trials have been conducted with a total of 528 patients with previously untreated small-cell lung cancer. Trials I to III were randomized phase III studies testing the value of prophylactic cranial irradiation, immunotherapy, and etoposide, respectively. They were done in the setting of combined modality treatment with the same local chest radiotherapy (3,000 rad in 10 fractions) and combined agent chemotherapy using a nucleus of CAV (cyclophosphamide, doxorubicin, vincristine). Trial IV was a pilot study evaluating sequential hemibody radiotherapy in a combined modality treatment program with CAV. Overall, the best treatment results to date have been observed following the combination of etoposide with CAV in trial III, particularly for patients with extensive disease. This combination with or without other agents also appears to be a common component of many trials that have reported particularly good survival results in this disease.
Antineoplastic Combined Chemotherapy Protocols↗
Cure of hepatic candidiasis in acute leukemia.
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Adult↗
Combination vincristine and VP-16-213: evaluation of drug sequence.
The combination of vincristine and VP-16-213 has been found to have synergistic antitumor activity in a murine system in vivo when the sequence of drug administration was vincristine followed by VP-16-213. To investigate the potential influence of drug scheduling on this synergistic combination, the reverse sequence of drug administration was evaluated. DBA/2 mice were inoculated with 10(6) P-388 murine leukemia cells, after which saline only, VP-16-213 only, vincristine only, or VP-16-213 followed at various time intervals by vincristine, were administered. Probable cure (survival greater than 60 days) was observed in 0/20, 0/20, 0/120, and 46/115 (40%), respectively (p less than 0.001). The proportion of animals attaining probable cure was greatest in the group receiving vincristine 4-72 hours after VP-16-213 (40-50%). Similar results had been obtained previously with the reverse drug sequence. In this animal model, the synergistic antitumor activity of vincristine and VP-16-213 does not appear to be schedule-dependent with respect to the sequence of drug administration.
Animals↗
A randomized trial of adjuvant chemotherapy and immunotherapy in Stage I and Stage II cutaneous melanoma. An interim report.
Seventy patients with Stage I and II malignant melanoma were randomized to treatment with either intravenous dacarbazine alone or intravenous dacarbazine plus intradermal injection of the methanol-extracted residue of bacillus Calmette-Guerin (BCG). Analysis of treatment failed to reveal a statistically significant difference between these two forms of treatment in Stage I and II patients. It is possible that chemoimmunotherapy may increase survival in Stage II patients, but this possibility should be interpreted with caution.
Adult↗
Phase II trial of vincristine infusion in acute leukemia.
A phase II trial of prolonged IV infusions of vincristine was conducted in 21 patients with refractory acute leukemia. Patients received 0.25-0.50 mg/m2 by infusion daily for 5 days after an initial 0.5-mg bolus. A partial response was observed in one of two patients with acute lymphoblastic leukemia. Of 14 patients with acute nonlymphoblastic leukemia, a complete response lasting for 2.5 months occurred in one patient and a partial response lasting 1.3 months was observed in a second. No objective responses were noted in five patients with blast crisis of chronic granulocytic leukemia. Nonhematologic toxicity was minimal and, when present, generally consisted of a feeling of weakness; constipation, mucositis, and areflexia were also observed. Hematologic toxicity consisted mainly of mild to moderate reduction of platelets in most patients; marked thrombocytopenia (less than 50,000/mm3) occurred in two patients whose pretreatment platelet count was greater than 100,000/mm3. Although generally well tolerated, prolonged infusion of vincristine appears to have limited activity in the treatment of refractory acute nonlymphoblastic leukemia and blast crisis of chronic granulocytic leukemia; further evaluation is needed in acute lymphoblastic leukemia refractory to conventional bolus injection.
Acute Disease↗
Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis.
Sequential hemibody irradiation (SHB) was integrated with combination chemotherapy and local irradiation (LRT) in the induction and consolidation phases of a therapeutic protocol for small cell lung carcinoma (SCLC). Forty-one previously untreated patients were entered into this program. Among 38 evaluable patients (20 with limited disease [LD] and 18 with extensive disease [ED], the overall response rate was 63% (90% in LD and 33% in ED patients). The estimated overall survival is 8.1 months. The major toxicity has been myelosuppression--especially thrombocytopenia. The frequency of previously described "acute radiation syndromes" and radiation pneumonitis associated with hemibody irradiation have been substantially decreased at the current dosage with premedication and shielding techniques. The integration of SHB as a systemic therapy with combination chemotherapy and LRT is a feasible program for sequential administration of non-cross-resistant agents in SCLC and may be beneficial in patients with limited disease.
Adult↗
Phase II study of vincristine infusion in refractory small cell carcinoma of the lung.
Fifteen patients with extensive refractory small cell carcinoma of the lung received prolonged intravenous infusion of vincristine. All but one patient had previously been given vincristine by conventional bolus injection. Treatment consisted of a 0.5-mg bolus injection followed immediately by 0.25 mg/m2/day infusion which was continued for 5 days. Toxicity in general was minimal, but rapidly progressive disease precluded adequate assessment in the majority of patients. No objective responses were observed. Infusion of vincristine does not appear to be an efficacious salvage treatment for this disease.
Adult↗
Single agent vincristine by infusion in refractory multiple myeloma.
A phase 2 trial of vincristine infusion was conducted in a group of 21 patients with refractory multiple myeloma. Patients were generally heavily pretreated with radiotherapy and chemotherapy. Vincristine was given intravenously (IV) as a 0.5 mg bolus and followed immediately by infusion of 0.25 to 0.50 mg/m2/d for 5 days. Courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Objective responses (partial) were noted in two patients (10%), both of whom were administered 0.5 mg/m2/d infusions. Response durations were brief (2.2 and 1.2 months). Toxicity consisted of neurotoxicity and myelosuppression. In addition to the occurrence of paresthesias and myalgias, ileus (two cases) and moderately severe loss of motor function (two cases) were observed. The mean lowest WBC count following treatment was 2.67 X 10(3)/microL v 3.96 X 10(3)/microL pretreatment (P = .008). The mean lowest platelet count was 75.0 X 10(3)/microL v 106.8 X 10(3)/microL pretreatment (P = .008). Vincristine infusion appears to have limited activity in the treatment of refractory multiple myeloma. Additionally, response durations were short lived and toxicity, both neurologic and hematologic, was appreciable.
Adult↗
Megestrol acetate v tamoxifen in advanced breast cancer: a phase III trial of the Piedmont Oncology Association (POA).
One hundred twenty-four patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally, four times daily, or tamoxifen 10 mg orally twice daily. If therapy failed patients were crossed over to the alternate treatment. Eligibility required that either the estrogen or progesterone receptor be positive or that both values be unknown, and that patients be at least 2 years postspontaneous menopause or over 50 years of age. Pretreatment characteristics were similar for both groups. Three patients had had previous hormonal therapy while one third had had chemotherapy. Objective response for evaluable patients based on strict UICC criteria was 29% with megestrol acetate and 31% with tamoxifen. Responses in patients with bone and soft tissue disease were similar for both regimens; however, 7 of 19 (37%) patients with visceral disease responded to tamoxifen but none of 18 (0%) responded to megestrol acetate. Response did not correlate with amount of estrogen or progesterone receptor. Unadjusted analysis of time to progression and survival showed no significant differences between regimens. With adjustment for pretreatment characteristics, patients on tamoxifen had a statistically significant prolongation of both of these parameters. Crossover data show 3 of 24 patients responding to tamoxifen after failure on megestrol acetate and 1 of 24 responding to megestrol acetate after failure on tamoxifen. However, crossover data should be viewed cautiously, as patients who are currently responding to initial treatment are those who would be most likely to respond to crossover therapy.
Aged↗
Sequential high-dose ara-C and asparaginase in the therapy of previously treated and untreated patients with acute leukemia.
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Aging↗
Interferon and doxorubicin in renal cell carcinoma.
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Adenocarcinoma↗
High-dose cyclophosphamide and 5-fluorouracil versus vincristine, doxorubicin, and cyclophosphamide in advanced carcinoma of the breast. A phase III study of the Piedmont Oncology Association (POA).
Forty-nine patients with advanced carcinoma of the breast who had received no prior chemotherapy were randomized to receive either high-dose cyclophosphamide (C) 1250 mg/M2 intravenously on day 1 and 5-fluorouracil (F) 600 mg/M2 intravenously on days 1 through 5 (CF), or vincristine (V) 1.5 mg/M2, doxorubicin (A) 50 mg/M2 and cyclophosphamide (C) 500 mg/M2 (VAC), all intravenously on day 1. Both regimens were repeated at 3-week intervals. Nine of 25 patients (36%) treated with CF and ten of 21 patients (48%) treated with VAC showed a complete or partial response as defined by the (UICC) guidelines. The estimated median time to progression for all patients was 3.5 months for CF and 6.0 months for VAC, with the median time to progression for responding patients being 8.5 months on CF and 6.3 months on VAC. Estimated survival is also similar for the two regimens. Ten of the patients treated with high-dose CF experienced septic episodes and four died. Toxicity on the CF arm necessitated premature closure of the study, and thus full statistical comparison of the efficacy of the two regimens cannot be made.
Antineoplastic Combined Chemotherapy Protocols↗
Treatment of advanced non-Hodgkin's lymphoma with vincristine infusion.
Twenty-five patients with a variety of histologic types of advanced non-Hodgkin's lymphoma refractory to previous chemotherapy were entered into a trial of vincristine infusion. Patients received 5-day courses of vincristine 0.25 mg/m2/day by continuous intravenous infusion after an initial 0.5 mg intravenous bolus injection. Courses were repeated every 3 weeks. Objective responses were observed in nine patients (36%), all of whom had previously received vincristine given by conventional bolus injection. A complete response occurred in a patient with diffuse mixed histiocytic lymphocytic lymphoma, and partial responses were observed in eight patients with the following histologic types: diffuse poorly differentiated lymphocytic (4); nodular poorly differentiated lymphocytic (2); diffuse mixed histiocytic lymphocytic (1); and diffuse histiocytic (1). Duration of response lasted from 1.2 to 16.2 months (mean, 4.4 months). The principal complication of therapy was mild-to-moderate neurotoxicity; this occurred in 12 patients (48%) who received a total of 54 courses of vincristine infusion. Hematologic toxicity was minimal and nausea/vomiting did not occur. Vincristine infusion may afford palliation for patients with advanced non-Hodgkin's lymphomas who have become refractory to standard chemotherapeutic regimens even if they have received prior vincristine by conventional bolus injection. These data suggest the possibility of enhancing the therapeutic efficacy of vincristine in the treatment of non-Hodgkin's lymphoma by use of an infusion technique.
Adult↗
Arterial thromboembolic complications of peritoneovenous shunting for malignant ascites.
Peritoneovenous shunting for the treatment of malignant ascites has become increasingly popular. This technique can be complicated by tumor embolization, congestive heart failure, and disseminated intravascular coagulation. Arterial thromboembolism has been encountered in two patients following LeVeen shunt insertion. Recurrent bilateral femoral artery thromboemboli and a cerebrovascular accident occurred in one patient and cerebrovascular thromboembolism developed in a second patient. Major arterial embolization is potentially a serious, although infrequent, complication of peritoneovenous shunting in patients who have malignant ascites.
Aged↗
Detection of brain metastasis at diagnosis of small cell carcinoma of the lung.
As a part of the initial evaluation of previously untreated patients with small cell carcinoma of the lung, radionuclide and/or computerized tomographic (CT) scanning of the brain was performed. Evidence of metastatic brain disease was documented in 10 (9%) patients (9 by CT and 1 by radionuclide scanning). CT was abnormal in 2 patients who had no evidence of brain metastasis by radionuclide scan. The detection of brain metastasis resulted in upstaging of 6 neurologically asymptomatic patients who had no other extrathoracic disease. Evaluation of the brain with CT is recommended as part of the initial staging of patients with small cell carcinoma of the lung.
Brain Neoplasms↗
Improved tolerance of vincristine by glutamic acid. A preliminary report.
In a murine model system, glutamic acid has demonstrated host protective properties during administration of vincristine (VCR). Subsequently, glutamic acid has been evaluated in patients receiving VCR during adjuvant chemotherapy for stage II carcinoma of the breast. The cumulative VCR dosage and toxicities incurred in 16 patients receiving glutamic acid have been compared to those observed in 88 patients who previously received VCR without glutamic acid in the same chemotherapy program. All patients received VCR 1.0 mg/m2 weekly for 6 weeks with dose modification for neurotoxicity. Treatment patients received glutamic acid 1.5 grams p.o. daily in three divided doses during the induction course. Of the 16 treatment patients, 9 (56%) received 100% ideal dosage of VCR during induction therapy whereas only 24 of 88 (27%) comparison patients attained this dosage level (p less than .025). Gastrointestinal and hematologic toxicities were similar in both groups. These preliminary results suggest the need for an expanded trial of this agent during administration of VCR.
Antineoplastic Combined Chemotherapy Protocols↗
Pharmacokinetics of vindesine bolus and infusion.
The pharmacokinetics of vindesine were investigated during treatment of 15 patients with progressive malignancies refractory to conventional treatment. Patients were administered one of three IV dose schedules: 3.0 mg/m2 bolus injection, 1.2 mg/m2/day infusion for 5 days, or 2.0 mg/m2/day infusion for 2 days. Concentrations of the drug in the serum and urine were determined by radioimmunoassay. Serum concentrations were highest (5 X 10(-7) M) in patients receiving a bolus injection, but fell to nondetectable levels by 48 h in four of five patients (terminal t1/2 15.0 +/- 9.4 h). Compared with bolus injection, 1.2- to 1.4-fold greater areas under the blood concentration curve were observed during infusions of 2.0 mg/m2 and 1.2 mg/m2. Whereas steady-state concentrations (approximately 1 X 10(-8) M) were maintained throughout the infusion of 1.2 mg/m2/day progressively increasing serum levels were observed during the infusion of 2.0 mg/m2/day. Serum concentrations fell rapidly following discontinuation of the 2.0-mg/m2 infusion, but were somewhat more sustained in the 1.2-mg/m2 infusion group. The average urinary excretion was similar for each dose-schedule (8%-11% of the total dose). The pharmacokinetics of vindesine are influenced by variations in dose schedule.
Adult↗