Vinblastine in the management of testicular cancer.
TL;DR: The activity of vinblastine alone and in combination with melphalan was studied in 32 patients with metastatic testicular neoplasia of germinal origin this article.
Abstract: The activity of vinblastine alone and in combination with melphalan was studied in 32 patients with metastatic testicular neoplasia of germinal origin. There was a total of 16 objective responses. Twenty-one patients received 0.4 to 0.8 mg/kg of vinblastine intravenously in 2 or 3 equal daily fractions, which was repeated at 3- to 4-week intervals. There were 4 complete and 7 partial responses, the longest being 42+ months. The combination of vinblastine, 3.5 to 4.0 mg/kg intravenously in one dose, followed in 24 to 48 hours with melphalan, 0.5 to 1.0 mg/kg in 500 ml of 5% glucose in water, was given to 11 patients. Treatment was repeated at 4- to 6-week intervals. There were 2 complete and 3 partial responses, the longest being 66+ months. There was no significant difference in the number of responses or the median duration of response between the 2 treatment groups. Partial responses were seen in all histologic groups. Complete responses were limited to embryonal carcinoma, pure or mixed with seminoma, and teratoma, pure or mixed with embryonal carcinoma, seminoma or choriocarcinoma (Groups II and IV of Dixon and Moore). Statistical analysis of survival data shows a highly significant difference (P < 0.001) between responding and nonresponding patients.
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TL;DR: In this paper, a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin was used to treat 50 patients with disseminated testicular cancer.
Abstract: Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered inevaluable due to early death. This chemotherapy regimen produced 74% complete and 26% partial remissions. Furthermore, five patients with partial remission became disease-free after surgical removal of residual disease, producing an overall 85% disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable, although there were two drug-related deaths during this period. Thirty-eight of these patients remain alive and 32 remain alive and disease-free at 6 + to 30 + months. We believe this regimen represents a major advance in the management of patients with disseminated testicular cancer.
1,355 citations
01 Jan 2002
TL;DR: Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin, producing an overall 85% disease-free status.
Abstract: (Reprinted with permission from Ann Intern Med, 87: 293–298, 1997) Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered inevaluable due to early death. This chemotherapy regimen produced 74% complete and 26% partial remissions. Furthermore, five patients with partial remission became diseasefree after surgical removal of residual disease, producing an overall 85% disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable, although there were two drug-related deaths during this period. Thirty-eight of these patients remain alive and 32 remain alive and disease-free at 6 to 30 months. We believe this regimen represents a major advance in the management of patients with disseminated testicular cancer. Although testicular cancer accounts for only 1% of all malignant tumors in men, it ranks first in incidence of cancer deaths in the 25 to 34 age group. 1 Thus cancer of the testis has a significant impact on the social, economic, and emo
1,340 citations
TL;DR: Gastrointestinal, renal, audiologic, and relatively minor hematologic toxicities may be encountered, but promising methods have been developed to increase the therapeutic index of DDP.
Abstract: Cis-diamminedichloroplatinum (II) (DDP) leads the series of platinum coordination complexes, a new class of cytotoxic agents. The antitumor and toxic effects of this drug are discussed. It has displayed encouraging results in testicular tumors. The drug's therapeutic effectiveness has also been recognized in a variety of other solid tumors, particularly ovarian, bladder, and head and neck malignancies. Gastrointestinal, renal, audiologic, and relatively minor hematologic toxicities may be encountered, but promising methods have been developed to increase the therapeutic index of DDP.
434 citations
Journal Article•
TL;DR: This third-generation study tested the hypothesis of whether maintenance vinblastine was necessary to ensure optimal cure rates in disseminated testicular cancer and demonstrated that cure in a far-advanced cancer could be achieved with only 12 weeks of therapy (remission induction) because the relapse rate in such patients was only 7%.
Abstract: The combination of platinum, vinblastine, and bleomycin was first used at Indiana University in 1974. Thirty of 47 patients (64%) survived for 5 years, and 27 (57%) are currently disease free (NED) and cured of their neoplasm. From 1976 to 1978, 78 consecutive patients were entered on a random prospective study that indicated that equal therapeutic results could be achieved with a lower dosage (0.3 mg/kg) of vinblastine. Fifty-two (67%) patients are continuously NED, and 57 (73%) are currently NED for 2 or more years. Our third-generation study, done in conjunction with the Southeastern Cancer Study Group, tested the hypothesis of whether maintenance vinblastine was necessary to ensure optimal cure rates in disseminated testicular cancer. One hundred thirteen patients entered this maintenance study, and the results demonstrated that cure in a far-advanced cancer could be achieved with only 12 weeks of therapy (remission induction) because the relapse rate in such patients was only 7%. The cure rate for patients presenting with locoregional disease (Stages A and B) should approach 100%. Platinum, vinblastine, and bleomycin will regularly produce a 70% complete remission rate, and a further 10% of patients will be rendered NED with surgical resection of residual disease. The relapse rate with four courses of remission induction therapy in a large cooperative group study (Southeastern Cancer Study Group) was only 7%. The high success rate in disseminated disease has allowed the option of high cure rate in Stage B disease (positive retroperitoneal nodes) with or without adjuvant chemotherapy. At Indiana University, 137 patients have been followed with Stage A and B nonseminomatous testicular cancer from 1973 to 1979 with a minimum follow-up of 2 years, and currently 135 are alive and well. Successful treatment strategies in testicular cancer have yielded a cure rate unparalleled in cancer treatment.
352 citations
Cites background from "Vinblastine in the management of te..."
...Later in the same decade, mithramycin (12) and vinblastine (21) were two other antineoplastic agents capable of achieving similar therapeutic results....
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...VP-16 has more impressive single-agent activity as sec ondary or tertiary therapy than vinblastine did as primary singleagent activity (21)....
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TL;DR: Cisplatin remains as the standard platinum analog in the treatment of patients with good-risk GCTs and two-drug therapy with EC using this dose and schedule was inferior to therapy with EP.
Abstract: PURPOSEThis multicenter, randomized phase III clinical trial evaluated the efficacy of etoposide plus carboplatin (EC) versus etoposide plus cisplatin (EP) in good-risk germ cell tumor (GCT) patients.PATIENTS AND METHODSBetween October 1986 and December 1990, 270 patients with good-risk GCTs were randomized to receive four cycles of either EP or EC. The etoposide dose in all patients was 100 mg/m2 on days 1 through 5. EP patients received cisplatin at 20 mg/m2 on days 1 through 5 and therapy was recycled at 21-day intervals. For EC patients, the carboplatin dose was 500 mg/m2 on day 1 of each cycle and the EC recycling interval was 28 days.RESULTSTwo hundred sixty-five patients were assessable: 131 patients treated with EC and 134 treated with EP. One hundred fifteen of 131 assessable patients (88%) treated with EC achieved a complete response (CR) versus 121 of 134 patients (90%) treated with EP (P = .32). Sixteen patients (12%) treated with EC relapsed from CR versus four patients (3%) treated with EP. ...
314 citations
References
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TL;DR: A phytochemical investigation of the plant Vinca rosea Linn has demonstrated that a number of alkaloidal substances can be obtained with antitumor activity, including vinblastine, vincristine, and vinrosidine, which are capable of prolonging and/or “curing” mice of the P-1534 leukemia.
Abstract: Summary A phytochemical investigation of the plant Vinca rosea Linn. has demonstrated that a number of alkaloidal substances can be obtained with antitumor activity. Over 30 alkaloids have been obtained, of which four—vinblastine, vinleurosine, vincristine, and vinrosidine—are known definitely to be active. Chemically these compounds are closely related to one another and to two monomeric alkaloids, vindoline and catharanthine. The structure of these latter two compounds has been determined, and partial structures for the biologically active alkaloids have been proposed. They represent a new class of large complex dimeric alkaloids containing both indole and dihydroindole moieties. Experimentally, a strain-specific, transplantable, acute, lymphocytic leukemia (P-1534) carried in DBA/2 mice served as a bioassay for obtaining these compounds and for predicting their clinical activity. Vinblastine, vincristine, and vinrosidine are capable of prolonging and/or “curing” mice of the P-1534 leukemia even when therapy is delayed until a near-terminal state of generalized disease. Resistance to an additional challenge of leukemic cells has been observed in these “cured” animals. Parenteral administration of vincristine has been demonstrated to “cure” mice given intracranial implants of the P-1534. The experimental tumor spectrum and toxicological studies are presented and discussed. Biochemical studies performed to date do not reveal any effect on cellular respiration, glycolysis, protein or nucleic acid synthesis. The mechanisms of action of these compounds, which may differ within the group as well as from those of other known agents, remain to be determined. Only two of these compounds, vinblastine and vincristine, have received extensive clinical evaluation. In spite of their close similarity, chemically, a somewhat different group of human neoplasms responds to these compounds, and there has been a singular lack of cross-resistance between these two drugs and any other oncolytic drug now in wide use. Vinblastine has proved effective in chorioepithelioma, Hodgkin9s disease, and other lymphomas, and a number of beneficial results have been obtained in carcinoma of the breast and bronchus. In addition, there have been smaller numbers of a variety of other neoplasias reported as responding to this compound. Vincristine has been striking in its ability to induce complete hematological remission of the acute leukemias of childhood, both lymphocytic and myelogenous in type. Responses have also been reported in a number of other malignancies. The problems and obstacles encountered in obtaining a full realization of the clinical efficacy of these new types of oncolytic compounds are discussed in addition to areas of clinical application other than those previously reported.
528 citations
TL;DR: Tumor regression was associated with a fall of urinary chorionic gonadotropin titer and side-effects occurred but proved reversible, and they were accepted as hazards of the treatment because of the striking improvement obtained in some cases.
Abstract: Advanced cancer of the testis was treated in 36 patients with different combinations of an alkylating agent, an antimetabolite, and the antitumor antibiotic actinomycin D. Of 23 patients treated with the three classes of drug in combination, 12 gave evidence of tumor regression. Of 9 patients treated with an alkylating agent and actinomycin D, 2 showed resolution of pulmonary metastases. Of 8 patients treated with 6-mercaptopurine (6-MP) and 6-diazo-5-oxo-L-norleucine (DON), one responded. Of the 15 respondents, 10 had choriocarcinoma with or without embryonal carcinoma and teratocarcinoma or both. Tumor regression was associated with a fall of urinary chorionic gonadotropin titer. Side-effects occurred but proved reversible, and they were accepted as hazards of the treatment because of the striking improvement obtained in some cases.
366 citations
TL;DR: Using polarized light, Griseofulvin was easily the best agent for rapid, reversible, and repeated dissolution of the spindle in mitotic spindles of living Pectinaria oocytes.
Abstract: Using polarized light we have studied the effects of various mitotic poisons on mitotic spindles of living Pectinaria oocytes; we have studied fixed specimens with phase and electron microscopy. Vinblastine caused attrition and eventual disappearance of spindle structure as rapidly as did colcemid, and subsequent recovery from this treatment was at least as fast as that from colcemid. Griseofulvin, however, was easily the best agent for rapid, reversible, and repeated dissolution of the spindle. Agents that arrest metaphase may act on nondividing cells by interfering with the organization of other gelated structures.
249 citations
Journal Article•
TL;DR: Preliminary studies in vitro demonstrated that certain compounds were capable of reversing the growth-inhibitory activity of VLB against human monocytic leukemia cells, and VLB and leurosine are representatives of a new class of clinically active antitumor compounds which may interfere with the cellular metabolic pathways leading from glutamic acid to urea, and from glutic acid to the citric acid cycle.
Abstract: Summary The experimental activity of a new clinically confirmed antitumor compound, Vincaleukoblastine (C46H58O9N4), (VLB) as the sulfate has been described. Greatest activity was seen against the P-1534 acute lymphocytic leukemia in DBA/2 mice. Late as well as early stages of this leukemia were significantly affected by this compound. No synergistic or additive effects have been observed in combination therapy with other antitumor compounds. A second indole-indoline alkaloid, leurosine, isomeric with VLB, has also been obtained from Vinca rosea Linn, with similar demonstrable experimental antitumor activity. Two other alkaloids, vindoline (C25H32O2) and catharanthine (C21H24O2N2), also obtained from Vinca rosea, were devoid of antitumor activity singly or in equimolar concentrations, but have been postulated as the biogenetic precursors of VLB and leurosine. Preliminary studies in vitro demonstrated that certain compounds were capable of reversing the growth-inhibitory activity of VLB against human monocytic leukemia cells. These compounds were coenzyme A, aspartic acid, tryptophan, α-ketoglutaric acid, ornithine, citrulline, arginine, and glutamic acid. VLB and leurosine are representatives of a new class of clinically active antitumor compounds which may interfere with the cellular metabolic pathways leading from glutamic acid to urea, and from glutamic acid to the citric acid cycle.
158 citations