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Biomedical subjects

D F Bajorin

Publications and source records attributed to D F Bajorin.

At least 73 records · Page 4Linked to original sources
PubMed1994

Advanced seminoma: treatment results, survival, and prognostic factors in 142 patients.

PURPOSE: To investigate the efficacy of chemotherapy and to assess the relationship between selected pretreatment characteristics and survival in patients with advanced seminoma. PATIENTS AND METHODS: One hundred forty-two patients with advanced seminoma treated with platinum-based chemotherapy were the subject of this study. Treatment regimens included cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6) (45 patients), a six-cycle regimen of VAB-6 alternating with etoposide and cisplatin (two patients), cisplatin and etoposide (60 patients), and etoposide and carboplatin (35 patients). RESULTS: One hundred thirty of 140 (93%) assessable patients treated with platinum-based therapy achieved a favorable response (complete response or a partial response with negative serum tumor markers). One hundred twenty-five patients (88%) are alive and 120 (86%) remain progression-free at a median follow-up duration of 43 months. Fifty-seven of 60 patients (95%) who were treated with cisplatin and etoposide achieved a favorable response; 55 (92%) remain progression-free. The relative risks of death or of an event (death or relapse) related to human chorionic gonadotropin (HCG) elevation were 1.8 (P = .04) and 1.96 (P = .001), respectively. The relative risks of death or of an event associated with lactate dehydrogenase (LDH) elevation were 2.6 (P = .05) and 2.7 (P = .02), respectively. All 19 patients with a mediastinal primary tumor site achieved a complete response, and 18 of 19 (95%) remain progression-free. CONCLUSION: Four cycles of cisplatin and etoposide is highly effective therapy for seminoma and is the standard therapy at our center. Elevation of the serum markers HCG and LDH were of prognostic significance, while an extragonadal primary tumor site was not associated with an adverse prognosis. Studies of tumor biology, including genetic analysis, are ongoing to determine other parameters that may correlate with response and survival.

Adolescent↗
PubMed1994

Phase II trial of paclitaxel shows antitumor activity in patients with previously treated germ cell tumors.

PURPOSE: A trial of paclitaxel was conducted in patients with previously treated germ cell tumors (GCT). As the identification of new agents in GCT may be compromised by restricting entry criteria to heavily pretreated patients, an alternative trial design was used in which eligibility was restricted to patients with limited prior therapy. PATIENTS AND METHODS: Patients were eligible if their prior therapy was limited to one cisplatin-based regimen or < or = six cycles of prior cisplatin-based therapy. Paclitaxel 250 mg/m2 was administered by continuous infusion over 24 hours every 21 days. The dose of paclitaxel was modified for each patient based on toxicity. Granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg/d was administered during nadir periods. RESULTS: Thirty-one patients were treated; eight patients (26%) achieved a partial (n = 5) or a complete (n = 3) response. Responses were achieved in patients who had failed to respond to treatment with cisplatin, ifosfamide, and etoposide, and in patients with poor prognostic features, ie, mediastinal primary tumor site and patients with a best prior response of an incomplete response to cisplatin therapy. One complete responder remains continuously free of disease at 13+ months and one of the five patients who achieved a partial response remains progression-free at 14+ months. CONCLUSION: Paclitaxel has antitumor activity in GCT and warrants continued study in combination chemotherapy. Phase I/II trials will address its role in combination with cisplatin and ifosfamide and as a part of dose-intensive therapy. Furthermore, the study showed that a trial design in which eligibility criteria limits prior therapy was feasible, resulted in the identification of antitumor activity in a new agent, and may be considered in future trials for other promising new agents in GCT.

Adolescent↗
PubMed1994

Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up.

PURPOSE: To determine survival in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and to analyze prechemotherapy and postchemotherapy factors for prognostic significance. PATIENTS AND METHODS: The survival of 111 patients with T2-4N0M0 bladder cancer treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was assessed. Prechemotherapy and postchemotherapy factors were analyzed for correlation with survival. Factors found to be significant on univariate analysis were subjected to multivariate analysis using Cox's proportional hazards model. RESULTS: The median follow-up duration was 5.3 years. Initial tumor (T) stage (P = .0001), presence of ureteral obstruction (P = .0074), and presence of a palpable mass (P = .0039) were the only pretreatment factors found to be significant on univariate analysis. Postchemotherapy surgery was performed in 81 patients. In these cases, postchemotherapy clinical stage and pathologic stage were significant factors on univariate analysis. In the multivariate analysis, the initial prechemotherapy T stage and the postchemotherapy pathologic stage (pT stage) were the only two factors to demonstrate independent significance. An association between downstaging postchemotherapy and survival was observed for patients with extravesical disease (T < or = 3B) at the start of treatment. In this subset, the 5-year survival rate was 54% for patients with downstaging versus 12% for those without downstaging. This association was not observed for patients with bladder-confined disease (T < or = 3A) at presentation. CONCLUSION: The stage of bladder cancer at presentation and at postchemotherapy pathologic staging are independent prognostic factors for long-term survival in patients treated with neoadjuvant chemotherapy. Downstaging after neoadjuvant chemotherapy was associated with improved survival in patients with muscle-invasive bladder cancers, but only for those with extravesical disease (T > or = 3B) pretreatment. Randomized comparisons will be required to assess the impact of chemotherapy on overall survival.

Adult↗
PubMed1994

The management of patients with advanced germ cell tumors. Seminoma and nonseminoma.

Treatment strategies for germ cell tumors have evolved substantially during the last decade and are directed by pretreatment prognostic factors that include histology (seminoma versus nonseminoma), primary site of disease, serum concentrations of lactate dehydrogenase and human chorionic gonadotropin, and the number of metastatic sites of disease. Patients with a high likelihood of achieving a complete response to therapy (CR0.5) are considered "good risk" and receive three or four cycles of cisplatin-based chemotherapy. Patients with a low likelihood of achieving a complete response (CR0.5) are considered "poor risk" and should be considered for innovative treatment strategies with the intent of increasing the proportion of patients who are cured. One approach in patients with "poor risk" disease uses early treatment with high-dose chemotherapy and autologous bone marrow transplantation. In addition, effective salvage regimens are available for those patients who fail first-line therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Etoposide plus carboplatin or cisplatin in good-risk patients with germ cell tumors: a randomized comparison.

Two hundred sixty-five evaluable patients were randomized to receive either carboplatin/etoposide (131 patients) or cisplatin/etoposide (134 patients). Among the carboplatin-treated patients, 115 (88%) achieved a complete remission, compared with 121 (90%) of patients receiving cisplatin. In the carboplatin group, however, 16 patients (12%) relapsed following complete remission, in contrast to four (3%) of those receiving cisplatin. Thus, the total number of unfavorable events (incomplete response + relapse) was 32 (24%) in the carboplatin arm, compared with 17 (13%) in the cisplatin arm (P = .02). In addition, patients receiving carboplatin had a greater likelihood of being hospitalized for neutropenia and fever (P = .016) and had lower platelet nadirs (P < .001). It was concluded that carboplatin administered at the dose and schedule used in this clinical trial resulted in an inferior event-free survival rate and worse toxicity than cisplatin, and is not recommended for use in general practice.

Adolescent↗
PubMed1993

Suramin for germ cell tumors. In vitro growth inhibition and results of a phase II trial.

BACKGROUND: Several studies have indicated a role for specific growth factors in the differentiation or deregulated growth of germ cell cancers. One proposed mechanism of antitumor activity for suramin is the inhibition of these tumor-derived growth factors. METHODS: Based on these data, the effects of suramin were studied on the growth of a monolayer culture of two human teratocarcinoma cell lines, NT2/D1 and N2102ep. These represented one cell line that was sensitive (NT2/D1) and one that was resistant (N2102ep) to the differentiation agent retinoic acid. These studies were followed by a Phase II trial of suramin in patients with germ cell tumors. Patients were treated with a continuous infusion of suramin. Dosing was determined by a nomogram based on weekly serum concentrations. RESULTS: Suramin inhibited the growth of both cell types in a dose-dependent fashion at a concentration attainable in patient plasma. This provided the rationale for a clinical trial of suramin in patients with cisplatin-refractory germ cell tumors. Fourteen patients were treated, and no complete or partial responses were observed. One patient achieved a prolonged decline in serum alpha-fetoprotein level without change in the size of a bidimensionally measurable retroperitoneal mass for more than 11 months. CONCLUSIONS: Despite the results of the in vitro studies, a Phase II trial failed to demonstrate significant antitumor activity for suramin in patients with cisplatin-refractory germ cell tumors. Although the dosing of suramin by the nomogram was not associated with neurotoxicity, the time needed to achieve therapeutic levels was lengthy, and the levels, once achieved, were of short duration. Thus, an alternative means of administration, i.e., by intermittent bolus administration, is being investigated in trials for patients with prostatic carcinoma. The lack of definitive efficacy for suramin in this trial has led the authors to consider other agents in Phase II trials for cisplatin-refractory germ cell tumor.

Adult↗
PubMed1993

Phase II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.

BACKGROUND: Between 20% and 30% of patients with advanced germ cell tumors (GCTs) fail to have durable complete response to conventional cisplatin-based induction chemotherapy. However, third-line therapy with high-dose carboplatin and etoposide plus autologous bone marrow transplantation (AuBMT) has induced durable complete response in 10%-20% of patients with cisplatin-resistant GCT. PURPOSE: We conducted a phase II trial of first-line therapy that included high-dose carboplatin and etoposide plus AuBMT in untreated men with advanced GCTs and unfavorable prognosis (i.e., "poor-risk" patients). METHODS: Twenty-eight patients were treated with a conventional-dose, cisplatin-containing regimen (VAB-6 [cisplatin, vinblastine, bleomycin, cyclophosphamide, dactinomycin]) with or without high-dose carboplatin (1500 mg/m2) and etoposide (1200 mg/m2) plus AuBMT. Twenty-two of these patients were selected for treatment with two cycles of high-dose carboplatin and etoposide plus AuBMT when reduced clearance of serum tumor markers (alpha-fetoprotein [AFP] or human chorionic gonadotropin [HCG]), as evidenced by prolonged half-life (> 7 days for AFP and > 3 days for HCG), was observed after two cycles of conventional treatment. RESULTS: Fifteen (56%) of 27 patients considered assessable for response achieved a complete response (12 treated with high-dose chemotherapy plus AuBMT). Sixteen (57%) are alive; 13 (46%) are free of disease at a median follow-up of 31.2 months. For 36 cycles of high-dose chemotherapy, the median duration from bone marrow infusion until a granulocyte count of 0.5/mm3 and a platelet count of 50,000/mm3 was 16 days (range, 7-41 days and 8-30 days, respectively). Analysis showed a trend toward improved survival (P = .07) in patients treated with high-dose chemotherapy in this study, compared with 68 poor-risk patients with GCT treated with conventional-dose therapy alone in two earlier studies. Toxicity was not cumulative, and recovery of blood counts after AuBMT was generally rapid. CONCLUSIONS: Inclusion of high-dose carboplatin-containing chemotherapy in treatment of poor-risk GCT patients is feasible when serum tumor marker half-life is used to predict resistance to standard cisplatin-based therapy. High-dose therapy in this setting was well tolerated. IMPLICATIONS: Early use of a dose-intensive regimen may increase survival compared with conventional-dose therapy alone. Further studies with standard induction therapy and intensive high-dose therapy using hematopoietic growth factor support are warranted, followed by a randomized trial comparing this strategy with standard therapy.

Adolescent↗
PubMed1993

Prognostic factors in patients with metastatic malignant melanoma. A multivariate analysis.

BACKGROUND: Current methods to predict survival in patients with advanced, metastatic melanoma are limited. To determine clinical prognostic factors that accurately predict survival in patients with metastatic melanoma, a retrospective analysis was performed. METHODS: Clinical, hematologic, and biochemical pretreatment parameters from 284 patients entered on 18 Phase I and II clinical trials were analyzed to determine their prognostic effect on survival. A multivariate parametric regression based on the Weibull distribution was derived to estimate survival. RESULTS: Multivariate Weibull survival regression analysis showed that a simple model using the logarithm of the pretreatment values of lactate dehydrogenase and serum albumin, dichotomized as high and low, significantly and adequately predicted survival. A more complex multivariate model was also derived that involved the pretreatment platelet count, visceral organ involvement, and gender as additional factors. However, a larger study is needed to statistically validate such a model. CONCLUSIONS: The pretreatment values of serum lactate dehydrogenase and albumin are independent prognostic factors for survival in patients with metastatic melanoma. These two factors can be used to estimate survival of patients with advanced, metastatic melanoma and should be considered when designing melanoma trials in which survival is an endpoint.

Adult↗
PubMed1993

Dose-intensification of MVAC with recombinant granulocyte colony-stimulating factor as initial therapy in advanced urothelial cancer.

PURPOSE: This study was undertaken to define an escalated dose schedule of methotrexate, vinblastine, doxorubicin, and cisplatin (E-MVAC) with hematopoietic growth-factor support, to define the ability to deliver E-MVAC with recombinant human granulocyte colony-stimulating factor (rhG-CSF) on 21- and 14-day schedules, and to assess the ability of rhG-CSF to maintain dose-intensity over four cycles of chemotherapy. PATIENTS AND METHODS: Twenty-three patients with transitional-cell carcinoma of the urothelium received E-MVAC in a phase I investigation. Patients were treated on an every-21-day (n = 19) or every-14-day schedule of administration (n = 4), with rhG-CSF support. Delivered dose-intensity was calculated at the completion of four cycles of therapy relative to the planned administration of conventional MVAC (relative dose-intensity [RDI]). Peripheral-blood progenitor cell kinetics in these patients were studied prospectively. RESULTS: Overall, the delivered RDI was 33% higher than the previously reported delivered dose-intensity of MVAC without hematopoietic support (140% for doxorubicin, 51% for cisplatin). Dose-intensity was well maintained through three cycles of therapy, after which leukopenia and thrombocytopenia became dose-limiting. Sixty-nine percent of patients with measurable disease responded, four (25%) with complete remissions. In five patients treated beyond the maximally tolerated dose (MTD), a 50- to 200-fold increase in G-CSF, granulocyte-macrophage CSF (GM-CSF), and interleukin-3 (IL-3)-responsive peripheral-blood progenitor cells over baseline was observed after 9 days of rhG-CSF administration. CONCLUSION: These findings demonstrate the feasibility and limitations of dose intensification of M-VAC with rhG-CSF. While the overall impact of the increased drug administration can only be assessed in randomized comparisons, the results of the present trial suggest that escalations of the components of the four-drug regimen are unlikely to improve significantly the outcome for patients with advanced urothelial tract tumors.

Adolescent↗
PubMed1993

Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study.

PURPOSE: This 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 METHODS: Between 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. RESULTS: Two 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. Therefore, 32 patients (24%) who received carboplatin experienced an event (incomplete response [IR] or relapse) compared with 17 of 134 patients (13%) who received cisplatin (P = .02). At a median follow-up of 22.4 months, event-free and relapse-free survival were inferior for patients treated with EC (P = .02 and P = .005, respectively). No difference in overall survival was evident (P = .52). CONCLUSION: Two-drug therapy with EC using this dose and schedule was inferior to therapy with EP. Cisplatin remains as the standard platinum analog in the treatment of patients with good-risk GCTs. Carboplatin should be restricted to investigational trials in GCT.

Adolescent↗
PubMed1992

Phase II trial of suramin in patients with advanced renal cell carcinoma: treatment results, pharmacokinetics, and tumor growth factor expression.

Twenty-six patients with advanced renal cell carcinoma were treated with suramin administered by continuous infusion, with dosing determined by a nomogram. One patient achieved a partial response and five patients achieved a minor response or had stable disease for > 3 months. Toxicities included an immune-mediated thrombocytopenia in one patient and Staphylococcus sepsis that was not associated with neutropenia in five patients. Pharmacokinetic parameters were determined by the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit using a two-compartment open model and first-order rate elimination. This showed a wide interpatient variation in time to target level (median, 13.8 days), volume of distribution (median, 15.2 liters/m2), and t1/2-beta (median, 20.6 days). The patients who achieved a partial response, minor response, or stable disease had a slower elimination rate of suramin, compared to patients with progressive disease. Tumor specimens were obtained prior to therapy and were analyzed for the production of five different growth factor-specific RNA transcripts. These included transforming growth factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor types A and B. No difference in the pattern of growth factor expression was seen in tumors of responding and nonresponding patients. Suramin does not have significant antitumor activity in renal cell carcinoma. The wide variability in pharmacokinetics suggests that individual dosing should be used in future trials of suramin for treatment for other malignancies. Pertinent corollary studies of tumor biology and clinical pharmacology should be included whenever possible in clinical trials in patients with renal cell carcinoma.

Adult↗
PubMed1992

Treatment with high dose mouse monoclonal (anti-GD3) antibody R24 in patients with metastatic melanoma.

R24 is a mouse IgG3 monoclonal antibody that reacts with the ganglioside GD3 expressed by melanoma cells and other cells of neuroectodermal origin (e.g. adrenal medulla). Antitumour activity of R24 was demonstrated in initial phase I and pilot trials, but treatment was limited by urticaria at cumulative doses of 400 mg/m2. A trial exploring intensification of the dose of R24 was conducted in eight patients. Planned doses of R24 antibody were 800 and 1200 mg/m2 over 6-8 days by continuous i.v. infusion. All patients received concomitant therapy with hydroxyzine hydrochloride and cimetidine to minimize urticaria. One patient developed anaphylaxis, after which no further therapy was given. All patients developed peripheral blood lymphopenia and marked decreases in serum complement values during treatment, suggesting depletion of two possible effector mechanisms of the antitumour effects of R24. A vascular leak syndrome, manifested by weight gain, oedema and hypotension, was evident in seven patients during the initial 24-36 h of treatment. Serum sickness syndrome was observed in six of seven evaluable patients between days 5 and 8, coincident with the onset of the human anti-globulin response to R24. One patient given 1200 mg/m2 had a minor response (38% reduction in pelvic nodes) lasting 12 months. There was no detectable increase (by immunohistochemical staining) in deposition of R24 within tumour sites at doses used in this trial compared to that observed at doses of 240 and 400 mg/m2. The maximum tolerated dose was 800 mg/m2. Dose-limiting toxicity was manifest as reversible hypertension with end-organ symptoms (chest pain or visual field defects) in patients treated with a dose of 1200 mg/m2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A phase II trial of interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma.

PURPOSE: A phase II trial that used a regimen of interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) was undertaken to evaluate the efficacy of this combination in the treatment of metastatic renal cell carcinoma. PATIENTS AND METHODS: Thirty-four assessable patients were treated with one to two induction cycles of IL-2 administered by continuous intravenous (IV) infusion at a dose of 3 x 10(6) U/m2/d [corrected] for 4 days per week plus IFN-alpha administered by subcutaneous injection at a dose of 5 x 10(6) U/m2/d [corrected] for 4 days per week for 3 consecutive weeks. A maintenance regimen of IL-2 2 x 10(6) U/m2/d [corrected] given by continuous IV infusion for 5 days per week plus IFN-alpha subcutaneously at a dose of 6 x 10(6) U/m2/d [corrected] that was given 3 days per week for 3 weeks was administered for one to five cycles. Twenty-eight patients (82%) completed one to two induction cycles, and 14 patients (41%) received maintenance doses. RESULTS: Major responses were achieved in four patients (12%), which included one complete response (CR) in a bone metastasis. Responses were observed in patients both with and without prior nephrectomy as well as in a primary tumor. Toxicity was moderately severe and included two treatment-related deaths. CONCLUSIONS: In view of the minimal antitumor activity and associated toxicity, the combination of IL-2 and IFN-alpha in this trial cannot be recommended. The investigation of new cytokines and the identification of biologic prognostic factors for a response to immunologic therapy are essential.

Adult↗
PubMed1992

Ifosfamide-based chemotherapy for patients with resistant germ cell tumors: the Memorial Sloan-Kettering Cancer Center experience.

Sixty-six patients with germ cell tumors (GCTs) refractory to cisplatin plus etoposide/vinblastine-based therapy were treated with cisplatin, ifosfamide, and either etoposide (VIP) (50 patients) or vinblastine (VeIP) (16 patients). Sixty-two patients were evaluable for response. Twenty-one patients (34%) achieved a complete response (CR), 18 with chemotherapy alone and an additional three following surgical resection of viable tumor. Six of these patients have relapsed, and 15 (24%) remain in CR at a median follow-up of 13 months (range, 3+ to 41+ months). Three patients who achieved an incomplete response or relapsed from CR are disease free following additional salvage therapy; one patient underwent resection of a solitary metastasis and two received high-dose chemotherapy with autologous bone marrow rescue. Ifosfamide adds efficacy to cisplatin plus etoposide or vinblastine-based salvage therapy. Ifosfamide/cisplatin-based combinations should be considered in the first-line salvage treatment of germ cell tumors. The modest proportion of patients who achieve a durable CR following salvage therapy with VIP/VeIP emphasizes the need for early identification of treatment failure and more effective salvage therapy.

Adult↗
PubMed1992

Current perspectives on the role of adjunctive surgery in combined modality treatment for patients with germ cell tumors.

The role of surgery in patients with advanced GCT after chemotherapy has evolved substantially in the era of combined modality therapy. In evaluating patients for surgery after chemotherapy, the clinician must consider carefully the histology (seminoma v NSGCT) of the primary as well as the extent of the residual disease. In patients with seminoma, the size of residual disease (greater than or equal to 3 cm) permits selection of patients with a high incidence of residual malignancy. In contrast, criteria designed to select NSGCT patients in whom surgical intervention after chemotherapy can be avoided are associated with substantial error. A normal radiographic evaluation in patients with NSGCT does not indicate a negative pathology and the treating physician must consider the approximately 20% risk of residual teratoma or carcinoma despite evidence of a radiographic CR. Continued research is needed to improve the sensitivity and specificity of case selection for patients requiring surgery after chemotherapy in order to limit the toxicity of curative therapy in this patient population.

Antineoplastic Combined Chemotherapy Protocols↗