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Biomedical subjects

D F Bajorin

Publications and source records attributed to D F Bajorin.

At least 19 recordsLinked to original sources
PubMed2006

Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment.

BACKGROUND: Tumor proliferation and apoptosis may be influenced by the mdm-2 gene product, which can block the antiproliferative effects of p53. bcl-2, one of a family of related genes that regulates the apoptotic pathway, exhibits a negative influence. Both individual and cooperative effects of these gene products may affect the biological behavior of primary bladder cancers and long-term outcome to standard therapy. METHODS: This study retrospectively evaluated the association with survival of mdm-2, p53, and bcl-2 expression in 59 patients with muscle-invasive, node-negative transitional cell carcinoma (TCC) treated with neo-adjuvant chemotherapy followed by locoregional surgery. Each marker was defined as an altered phenotype if >or=20% malignant cells in the primary tumor exhibited staining; normal or minimal expression was defined as <20% cells exhibiting staining. RESULTS: Altered mdm-2, p53, and bcl-2 expression was observed in 37%, 54%, and 46% of patients, respectively. In single marker analysis, altered p53 expression correlated with long-term survival (P = 0.05) but mdm-2 (P = 0.42) or bcl-2 (P = 0.17) did not. In the multiple-marker analysis, a prognostic index simultaneously assessing mdm-2, p53, and bcl-2 correlated with survival (P = 0.01). The 5-year survival for patients in which all markers were normally expressed was 54% compared with 25% in those with all three markers aberrantly expressed. Patients with aberrant expression of either one or two markers had an intermediate 5-year survival (49%). There was no association of molecular markers either alone or in combination with pathologic downstaging after neo-adjuvant chemotherapy. CONCLUSION: The cooperative effects of phenotypes determined by mdm-2, p53, and bcl-2 expression may predict survival in patients with muscle-invasive TCC of the bladder.

Adult↗
PubMed2001

Predicting outcome to chemotherapy in patients with germ cell tumors: the value of the rate of decline of human chorionic gonadotrophin and alpha-fetoprotein during therapy.

PURPOSE: The prognostic significance of the rate of decline of the serum tumor marker alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) during the first two cycles of chemotherapy in germ cell tumor (GCT) patients was initially reported by us, but its value has been debated. We re-examined this issue in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification system and investigated the role of including in the analysis patients whose markers normalized early. PATIENTS AND METHODS: One hundred eighty-nine GCT patients with elevated AFP/HCG marker values treated with platinum-based chemotherapy between 1986 and 1998 were included in this analysis. Patients were classified as good, intermediate, or poor risk by the IGCCCG criteria and as having satisfactory or unsatisfactory marker decline. Risk and marker decline were correlated with response, event-free survival, and overall survival. RESULTS: Satisfactory marker decline predicted improved complete response (CR) proportion and event-free and overall survival (P <.0001). The CR proportion, 2-year event-free, and 2-year overall survival rates for patients with a satisfactory and unsatisfactory marker decline were 92% versus 62%, 91% versus 69%, and 95% versus 72%, respectively. Marker decline remained a significant variable for all three end points when adjusted for risk (P <.01) with the outcome differences most pronounced in the poor-risk group. CONCLUSION: The rate of marker decline during chemotherapy has prognostic value independent of risk and may play a significant role in the management of poor-risk patients. It is appropriate to include patients whose markers normalized early.

Adolescent↗
PubMed2001

Low-volume nodal metastases detected at retroperitoneal lymphadenectomy for testicular cancer: pattern and prognostic factors for relapse.

PURPOSE: To determine the incidence, pattern, and predictive factors for relapse in patients with low-volume nodal metastases (stage pN1) at retroperitoneal lymphadenectomy (RPLND) and identify who may benefit from chemotherapy in the adjuvant or primary setting. PATIENTS AND METHODS: Fifty-four patients with testicular nonseminomatous germ cell tumor had low-volume retroperitoneal metastases (pathologic stage pN1, 1997 tumor-node-metastasis classification) resected at RPLND, 50 of whom were managed expectantly without adjuvant chemotherapy. The dissection was bilateral in 12 and was a modified template in 38 patients. Retroperitoneal metastases were limited to microscopic nodal involvement in 14 patients. Follow-up ranged from 1 to 106 months (median, 31.4 months). RESULTS: Eleven patients (22%) suffered a relapse at a median follow-up of 1.8 months (range, 0.6 to 28 months). The most frequent form of recurrence was marker elevation in nine (18%) patients. Persistent marker elevation after orchiectomy and before retroperitoneal lymphadenectomy was a significant independent predictor of relapse (relative risk, 8.0; 95% confidence interval, 2.3 to 27.8; P =.001). Four of five (80%) patients with elevated markers (alpha-fetoprotein alone in three, alpha-fetoprotein and beta human chorionic gonadotropin in one) suffered a relapse, compared with seven of 45 (15.6%) patients with normal markers. CONCLUSION: Clinical stage I and IIA patients with normal markers who have low-volume nodal metastases have a low incidence of relapse and can be managed by observation only if compliance can be assured. In contrast, patients with elevated markers before retroperitoneal lymphadenectomy have a high rate of relapse and should be considered for primary chemotherapy.

Actuarial Analysis↗
PubMed2001

Role of postchemotherapy adjunctive surgery in the management of patients with nonseminoma arising from the mediastinum.

PURPOSE: To evaluate the role of postchemotherapy surgery in patients with nonseminomatous germ cell tumors arising from the anterior mediastinum. PATIENTS AND METHODS: Thirty-two patients with nonseminoma arising from a mediastinal primary site were treated on a clinical trial at our center, and they underwent postchemotherapy surgery. The results of postchemotherapy surgical resection, frequency of viable tumor found during postchemotherapy surgery, and prognostic factors for survival were assessed. RESULTS: Complete resection of all gross residual disease was achieved in 27 patients (84%). Histologic analysis of resected residua postchemotherapy revealed viable tumor in 66%, teratoma in 22%, and necrosis in 12% of the specimens. Viable tumor included embryonal carcinoma, choriocarcinoma, yolk sac carcinoma, seminoma, and teratoma with malignant transformation to nongerm cell histology (eg, sarcoma). Clinical characteristics associated with a shorter survival after surgery included the presence of viable tumor in a resected specimen (P =.003) and more than one site resected during surgery (P =.06). There were no statistically significant differences in survival for patients who underwent surgical resection with normal markers compared with patients with elevated serum tumor markers (P =.33). A trend toward shorter survival was found in patients with increasing tumor markers before surgery compared with patients with normal and declining serum tumor markers (P =.09). CONCLUSION: Surgical resection of residual mass after chemotherapy plays an integral role in the management of patients with primary mediastinal nonseminoma. Teratoma and viable tumor were found in the majority of resected residua after chemotherapy. Because patients who undergo conventional salvage chemotherapy programs rarely achieve long-term disease-free status, selected patients with elevated markers after chemotherapy are considered candidates for surgical resection.

Adolescent↗
PubMed2001

Post-chemotherapy surgery in patients with unresectable or regionally metastatic bladder cancer.

PURPOSE: We update our experience with post-chemotherapy surgery in patients with unresectable or lymph node positive bladder cancer. METHODS: Of 207 patients with unresectable or regionally metastatic bladder cancer 80 (39%) underwent post-chemotherapy surgery after treatment with a cisplatin based chemotherapy regimen. We assessed the impact of surgery on achieving a complete response to chemotherapy and on relapse-free survival. RESULTS: No viable cancer was present at post-chemotherapy surgery in 24 of the 80 cases (30%), pathologically confirming a complete response to chemotherapy. Of the 24 patients 14 (58%) survived 9 months to 5 years. Residual viable cancer was completely resected in 49 patients (61%), resulting in a complete response to chemotherapy plus surgery, and 20 (41%) survived. Post-chemotherapy surgery did not benefit those who failed to achieve a major complete or partial response to chemotherapy. Only 1 of the 12 patients (8%) who refused surgery remains alive. CONCLUSIONS: Post-chemotherapy surgical resection of residual cancer may result in disease-free survival in some patients who would otherwise die of disease. Optimal candidates include those in whom the pre-chemotherapy sites of disease are restricted to the bladder and pelvis or regional lymph nodes, and who have a major response to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Chemotherapy agents in transitional cell carcinoma: the old and the new.

Transitional cell carcinoma is a malignancy in which a number of single agents with different mechanisms of action are effective. Most older agents have limited activity, but several combinations are quite active. The most common regimens over the past 15 years were cyclophosphamide, doxorubicin, and cisplatin (CAP, CISCA); cisplatin, methotrexate, and vinblastine (CMV, MCV); and (methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC). Several new agents have been identified recently, including docetaxel, paclitaxel, gemcitabine, and ifosfamide. Combinations using these new agents now provide alternatives to the M-VAC combination that have much less toxicity and, in some instances, are used as multimodality therapy in patients with unresectable primary tumors without the degree of toxicity associated with older combinations of chemotherapy. Phase II and Phase III trials evaluating these new combinations are reviewed.

Antineoplastic Agents↗
PubMed2000

Ifosfamide, paclitaxel, and cisplatin for patients with advanced transitional cell carcinoma of the urothelial tract: final report of a phase II trial evaluating two dosing schedules.

BACKGROUND: A combination regimen of ifosfamide, paclitaxel, and cisplatin (ITP), recycled every 4 weeks, was reported in the treatment of previously untreated patients with advanced transitional cell carcinoma (TCC). This study sought to examine ITP at 3-week intervals to assess its feasibility and toxicity, compare the results for different schedules, and assess the impact of prognostic factors and postchemotherapy surgery on outcome. METHODS: ITP (ifosfamide 1.5 g/m(2) daily for 3 days, paclitaxel 200 mg/m(2) over 3 hours, and cisplatin 70 mg/m(2) on Day 1) was administered to patients with metastatic or unresectable TCC and was recycled every 4 weeks (for 30 patients) or 3 weeks (for 15 patients). Granulocyte-colony stimulating factor was given during each cycle. RESULTS: Thirty of 44 assessable patients (68%; 95% confidence interval, 52-81%) demonstrated a major response (10 complete responses [23%], 20 partial [45%]), with durations of response ranging from 4 to 36 months. At a median follow-up of 28 months, the median survival was 20 months. Eleven patients (25%) were disease free at last follow-up. Overall toxicity for the 15 patients whose treatment was recycled at 3 weeks was similar to that for patients treated every 4 weeks. Hematologic toxicity included anemia, thrombocytopenia, and febrile neutropenia. Febrile neutropenia was observed in 7 patients (16%) and in 3.3% of cycles of therapy. No Grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, renal insufficiency (11%), and neuropathy (9%). CONCLUSIONS: ITP is an active, well-tolerated regimen for previously untreated patients with TCC of the urothelial tract, resulting in a median survival of 20 months. Treatment can be recycled at 3-week intervals without enhanced toxicity.

Adult↗
PubMed2000

Exploring sequenced chemotherapy regimens in the treatment of transitional cell carcinoma of the urothelial tract.

This phase I trial evaluated the two-drug regimen doxorubicin and gemcitabine (AG) every other week for six cycles followed by ifosfamide, paclitaxel and cisplatin (ITP) every 3 weeks for four cycles in patients with transitional cell carcinoma of the urothelial tract. 15 patients were treated at five AG dose levels ranging up to doxorubicin 50 mg/m(2) and gemcitabine 2000 mg/m(2). The dose and schedule of ITP were constant at ifosfamide 1500 mg/m(2) on days 1-3 and paclitaxel 200 mg/m(2) and cisplatin 70 mg/m(2) on day 1. Granulocyte colony-stimulating factor was self-administered between all cycles of therapy. The trial determined that AG given at alternating weeks at doses of doxorubicin 50 mg/m(2) and gemcitabine 2000 mg/m(2) was feasible. After completion of the AG-ITP sequence, 9 of 14 (64%) evaluable patients had a major response (3 complete responses and 6 partial responses). Phase II investigation at the highest dose level is ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Phase II trial of pyrazoloacridine in patients with cisplatin-refractory germ cell tumors.

Thirteen patients with cisplatin-refractory germ cell tumors were treated on a Phase II trial with pyrazoloacridine. Pyrazoloacridine was given intravenously at 600 mg/m2 every three weeks. The median nadir leucocyte count was 2.5 cells/mm3, hemoglobin was 10.8 g/dl, and platelet count was 126,000 cells/m3. None of the thirteen evaluable patients achieved a major response. Pyrazoloacridine is not efficacious in the treatment of cisplatin-refractory germ cell tumors.

Acridines↗
PubMed2000

Phase II trial of pyrazoloacridine as second-line therapy for patients with unresectable or metastatic transitional cell carcinoma.

PURPOSE: A phase II trial of pyrazoloacridine (PZA) was conducted to assess its activity and toxicity in patients with advanced transitional cell carcinoma (TCC) refractory to or progressing after one prior cisplatin-, carboplatin- or paclitaxel- based regimen. PATIENTS AND METHODS: PZA at a dose of 750 mg/m2 was administered to 14 patients as a three-hour intravenous infusion on day 1 every 21 days. Premedication consisted of lorazepam 0.5-1.0 mg prior to each cycle to alleviate central nervous system toxicity. Reduction of subsequent doses was made for hematologic or central nervous system toxicity. RESULTS: Among fourteen patients evaluable for response, no responses were observed (0% response rate; 95% confidence interval 0% to 23%). The median duration of survival for all patients was 9 months with a median follow-up of 8.5 months. Toxicity to PZA included grade 3 or 4 neutropenia in 8/14 (57%) and grade 3 or 4 thrombocytopenia in 2/14 (14%). Non-hematologic toxicity was mild. CONCLUSIONS: PZA at this dose and schedule does not have significant single-agent activity in patients with TCC who have failed one prior regimen.

Acridines↗
PubMed2000

Retroperitoneal metastases in testicular cancer: role of CT measurements of residual masses in decision making for resection after chemotherapy.

PURPOSE: To determine the relative importance of computed tomographic (CT) measurements for the prediction of histologic findings in residual masses in patients with nonseminomatous testicular cancer. MATERIALS AND METHODS: Measurements of the maximum transverse size of retroperitoneal metastases before and after chemotherapy were available in 641 patients who underwent resection after chemotherapy while their levels of tumor markers were normal. Radiologic measurements of mass size and clinical characteristics (histologic findings in primary tumor and levels of alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase before chemotherapy) were related to histologic findings in the residual mass with logistic regression analysis. RESULTS: At resection, 302 patients had benign tissue, and 339 had residual tumor (mature teratomas or cancer). Tumor was more frequent in larger masses after chemotherapy but was unrelated to mass size before chemotherapy. Inclusion of the reduction in size significantly improved the logistic regression model, which included mass size after chemotherapy. This model was further improved with the addition of clinical characteristics. Areas under the receiver operating characteristic curves increased from 0.74 to 0.77 and 0.83 with these models. CONCLUSION: A small retroperitoneal mass after chemotherapy is an important predictor of benign histologic findings in residual masses in patients with nonseminomatous testicular cancer. However, better predictions can be made when the reduction in size and clinical characteristics are considered as well. Decisions regarding resection should be based on the combination of these characteristics rather than on only mass size after chemotherapy.

Area Under Curve↗
PubMed2000

Phase I evaluation of sequential doxorubicin gemcitabine then ifosfamide paclitaxel cisplatin for patients with unresectable or metastatic transitional-cell carcinoma of the urothelial tract.

PURPOSE: This phase I trial sought to evaluate the toxicity of and determine the maximum-tolerated dose (MTD) for the two-drug regimen doxorubicin and gemcitabine (AG) followed by the three-drug regimen of ifosfamide, paclitaxel, and cisplatin (ITP) in patients with unresectable or metastatic transitional-cell carcinoma. PATIENTS AND METHODS: Patients received AG every other week for six cycles followed by ITP every 3 weeks for four cycles. Five AG dose levels were investigated, up to doxorubicin 50 mg/m(2) and gemcitabine 2, 000 mg/m(2), to determine the MTD of the regimen. The dose and schedule of ITP were constant: ifosfamide 1,500 mg/m(2) (days 1 to 3); paclitaxel 200 mg/m(2) (day 1); and cisplatin 70 mg/m(2) (day 1). Granulocyte colony-stimulating factor was given between all cycles of therapy. RESULTS: Fifteen patients enrolled onto this phase I trial. AG was well tolerated at all dose levels, with no grade 3 or 4 myelosuppression. Toxicity experienced with ITP included grade 3 and 4 granulocytopenia in four patients and grade 3 nausea/vomiting in three patients. No grade 3 and 4 neurotoxicity was observed. Eight of 14 assessable patients experienced a major response to AG, including five of six patients treated at the two highest AG dose levels. After completion of AG-ITP, nine of 14 assessable patients had a major response (three complete responses and six partial responses). CONCLUSION: AG is a well-tolerated and active regimen. Sequential chemotherapy with AG-ITP is also well tolerated, and phase II investigation at the highest dose level is ongoing.

Aged↗
PubMed2000

Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients.

PURPOSE: To evaluate the efficacy and toxicity of sequential, dose-intensified chemotherapy with paclitaxel/ifosfamide and carboplatin/etoposide administered plus peripheral blood-derived stem-cell (PBSC) support for patients with germ cell tumors (GCT) who have unfavorable prognostic features in response to conventional-dose salvage programs. Carboplatin was dose escalated by target area under the curve (AUC; in [milligrams per milliliter] x minutes) among patient cohorts, and pharmacokinetic studies were performed for comparison. PATIENTS AND METHODS: Thirty-seven previously treated patients who had cisplatin-resistant GCT and unfavorable prognostic features for response to conventional-dose salvage therapy were treated. Two cycles of paclitaxel 200 mg/m(2) plus ifosfamide 6 g/m(2) were given 2 weeks apart with leukapheresis, followed by three cycles of carboplatin plus etoposide given 14 to 21 days apart with reinfusion of PBSCs. The dose of etoposide was 1, 200 mg/m(2), and the carboplatin target AUC ranged among cohorts from 12 to 32 (mg/mL) x min. Pharmacokinetic studies of carboplatin were performed for comparison of target to measured AUC. RESULTS: Twenty-one patients (57%) achieved a complete response and an additional two patients (5%) achieved a partial response with normal tumor markers; therefore, 23 (62%) achieved a favorable response. Eight patients relapsed, and 15 (41%) of the favorable responses remained durable at a median follow-up of 30 months. Myelosuppression was the major toxicity; 58% of carboplatin/etoposide cycles were associated with hospitalization for nadir fever. The AUC of carboplatin measured in serum was lower than the target AUC; this may be related to underestimation of the glomerular filtration rate used in the dosing formula. CONCLUSION: Dose-intense therapy with sequential, accelerated chemotherapy of paclitaxel/ifosfamide and carboplatin/etoposide administered with PBSC support was relatively well tolerated. The durable complete response proportion was substantial in patients with unfavorable prognostic features for achieving durable complete response to conventional-dose salvage programs. Optimal dosing of carboplatin in the high-dose setting warrants further investigation.

Adolescent↗
PubMed2000

Evaluation of drug delivery and survival impact of dose-intense relative to conventional-dose methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy in urothelial cancer.

The efficacy of dose-intense methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy relative to conventional-dose M-VAC in patients with advanced transitional cell carcinoma is unknown. The outcomes of 33 patients on two successive protocols using dose-intense M-VAC with granulocyte colony-stimulating factor (G-CSF) support were compared with those of 129 patients treated with conventional-dose M-VAC to assess for an impact of dose-intense therapy on long-term survival. The mean relative dose intensity of chemotherapy delivered to the dose-intense cohort was 55% higher than that delivered to the conventional-dose cohort (p = 0.0001). However, no significant differences were observed with regard to response proportion (72% vs. 76%), median survival (13.3 vs. 16.7 months, p = 0.31), or 5-year survival (16% vs. 15%). Growth factor support enabled a statistically significant increase in the delivered dose intensity of M-VAC chemotherapy, but no survival advantage relative to conventional-dose M-VAC was observed.

Adult↗
PubMed2000

Paclitaxel in the treatment of advanced urothelial cancer.

Median survival in patients with advanced urothelial carcinoma continues to be approximately 1 year following treatment with traditional cisplatin (Platinol)-based regimens, which have substantial toxicity. Thus, research is focusing on newer chemotherapeutic agents and novel combination regimens to improve outcomes and tolerability. Paclitaxel (Taxol) demonstrated one of the highest single-agent response rates (42%) in patients with advanced urothelial tumors, prompting extensive evaluation of combination regimens, including paclitaxel/platinum-based doublets or triplets. In many trials, carboplatin (Paraplatin) has been substituted for cisplatin to produce a more convenient, less toxic regimen. These trials have demonstrated that paclitaxel/platinum-based combinations are similar in efficacy to traditional cisplatin-based regimens and are generally better tolerated. Consequently, paclitaxel-based combinations (e.g., paclitaxel/carboplatin) are now considered alternative treatment options for patients with advanced disease, particularly those who are ineligible for clinical trials or are unable to tolerate standard cisplatin-based regimens. Paclitaxel/ifosfamide (Ifex)/cisplatin is another promising alternative regimen for patients who can tolerate cisplatin-based regimens. An ongoing phase III trial comparing paclitaxel/carboplatin and MVAC (methotrexate, vinblastine, Adriamycin, and cisplatin) should clarify the role of paclitaxel-based combinations. Paclitaxel-based combinations are also under evaluation in the adjuvant setting, and future trials may assess their potential role as neoadjuvant therapy or in combination with radiation therapy.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Phase II trial of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin in patients with unresectable or metastatic transitional cell carcinoma.

BACKGROUND: This study was undertaken to determine whether the use of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin as first-line therapy increases the proportion of major responders and overall survival in patients with unresectable or metastatic transitional cell carcinoma (TCC) of the urothelial tract. METHODS: Twenty-nine patients with histologically confirmed TCC received methotrexate at a dose of 1000 mg/m2 on Day 1 followed by leucovorin calcium rescue on Day 2 and vinblastine (3 mg/m2), doxorubicin (30 mg/m2), and cisplatin (70 mg/m2) (VAC) on Day 2. Therapy was recycled at 28-day intervals. RESULTS: Fourteen of 28 patients (50%; 95% confidence interval [CI], 31-69%) achieved a major response, including 6 pathologic or clinical complete responses (CR) and 8 partial responses (PR). Nine patients were rendered disease free after postchemotherapy surgical resection of residual disease (surgical CR), including five patients who had PR and four nonresponders to chemotherapy alone. Five of 18 patients with disease limited to lymph nodes attained CR, in contrast to only 1 of 10 patients with visceral metastatic disease. The median survival for the entire population was 13.6 months. CONCLUSIONS: The escalation of methotrexate to 1000 mg/m2 in combination with vinblastine, doxorubicin, and cisplatin did not result in a response proportion or median survival superior to that observed with standard dose M-VAC. As previously observed in a Phase II trial of M-VAC, only the attainment of CR was associated with prolongation of survival.

Adult↗