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Biomedical subjects

D F Bajorin

Publications and source records attributed to D F Bajorin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy.

PURPOSE: The variation in reported survival of patients with metastatic transitional-cell carcinoma (TCC) treated with systemic chemotherapy may be a consequence of pretreatment patient characteristics. We hypothesized that a prognostic factor-based model of survival among patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy could account for such differences and help guide clinical trial design and interpretation. PATIENTS AND METHODS: A database of 203 patients with unresectable or metastatic TCC was retrospectively subjected to a multivariate regression analysis to determine which patient characteristics had independent prognostic significance for survival. Patients were assigned to three risk categories depending on the number of unfavorable characteristics. Patient selection in phase II studies was addressed by developing a table of expected median survival for patient cohorts that had varying proportions of patients from the three risk categories. RESULTS: Two factors had independent prognosis: Karnofsky performance status (KPS) less than 80% and visceral (lung, liver, or bone) metastasis. Median survival times for patients who had zero, one, or two risk factors were 33, 13.4, and 9.3 months, respectively (P =.0001). The median survival time of patient cohorts could vary from 9 to 26 months simply by altering the proportion of patients from different risk categories. CONCLUSION: The presence of baseline KPS less than 80% or visceral metastasis has an impact on survival. Reporting the proportion of patients with zero, one, and two risk factors will facilitate understanding of the relevance of the median survival in phase II trials. Phase III trials should stratify patients according to the number of risk factors to avoid imbalance in treatment arms.

Adult↗
PubMed1999

Outcome of postchemotherapy surgery after treatment with methotrexate, vinblastine, doxorubicin, and cisplatin in patients with unresectable or metastatic transitional cell carcinoma.

PURPOSE: The role of postchemotherapy surgery for patients with metastatic transitional cell carcinoma (TCC) is controversial. We retrospectively analyzed our experience with patients who underwent postchemotherapy surgery after methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy to assess an impact on long-term survival. PATIENTS AND METHODS: This report is based on the retrospective analysis of 203 patients with unresectable primary tumors or metastatic TCC, previously reported in five trials of M-VAC chemotherapy. Fifty patients underwent postchemotherapy surgery for suspected or known residual disease. Characteristics of patients selected for surgery, results of surgery, and the impact of surgery on survival were assessed. RESULTS: In 17 patients, no viable tumor was found at postchemotherapy surgery, pathologically confirming a complete response to chemotherapy. Three patients had unresectable residual TCC. In 30 patients, residual, viable TCC was completely resected, which resulted in a complete response to chemotherapy plus surgery. Ten (33%) of these 30 patients remained alive at 5 years, similar to results observed for patients who attained a complete response to chemotherapy alone (41%). Analysis by baseline extent of disease suggested that patients with unresectable primary tumors or with metastases restricted to lymph node sites were most likely to survive for 5 years. CONCLUSION: Postchemotherapy surgical resection of residual cancer may result in 5-year disease-free survival in some patients who would otherwise succumb to disease. Optimal candidates include patients whose prechemotherapy sites of disease are restricted to the primary or lymph node sites and who have a major response to chemotherapy.

Adult↗
PubMed1999

Can p53 help select patients with invasive bladder cancer for bladder preservation?

PURPOSE: We evaluated whether the p53 status of invasive bladder cancer may help to select patients for treatment strategies aimed at bladder preservation. MATERIALS AND METHODS: A total of 111 patients with muscle invasive (T2 to 3N0M0) transitional cell carcinoma of the bladder received neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy. Of these patients 60 (54%) had a complete clinical response (TO) to M-VAC. We report the 10-year outcome for these 60 patients, stratified by p53 status (positive versus negative) and stage (T2 versus T3) of the primary bladder neoplasm, and type of surgery (bladder sparing versus cystectomy) after M-VAC. RESULTS: All 19 patients with T2 (organ confined) p53 negative tumors survived (16 after bladder sparing surgery and 3 after cystectomy) compared with 47% of 19 with T2 p53 positive tumors, 67% of 12 with T3 (extravesical) p53 negative tumors and 60% of 10 with T3 p53 positive tumors. CONCLUSIONS: Our study suggests that the bladder may be preserved for up to 10 years in patients with tumors confined to the bladder (stage T2) who lack detectable p53 if they respond completely to neoadjuvant chemotherapy. Patients with T3 bladder tumors or T2 p53 positive tumors are best treated currently with cystectomy.

Aged↗
PubMed1999

Toxicology and pharmacokinetics of intravesical gemcitabine: a preclinical study in dogs.

More active and well-tolerated agents are needed for the treatment of superficial bladder cancer. This study investigated intravesical gemcitabine to establish the toxicology and pharmacokinetics necessary for clinical trials. Beagle dogs (in groups of 2; n = 6) received 100 mg, 350 mg, or 1 g of drug by intravesical administration on alternate days three times/week for 4 weeks. Animals were observed for clinical signs of toxicity; gemcitabine levels and peripheral blood counts were taken three times weekly. The dogs were euthanized, and a full necropsy was performed at days 1 and 14 after the last dose. Intravesical gemcitabine was given at 100 mg (n = 2), 350 mg (equivalent to the 1000 mg/m2 human dose; n = 3), and 3.5 g (n = 1). i.v. gemcitabine was given at 350 mg (n = 2). Plasma samples drawn at time points up to 8 h were analyzed for systemic absorption and clearance of drug. Doses of 100 and 350 mg were well tolerated with no clinical side effects. Necropsies revealed normal bone marrow cellularity and normal bladder histology. At 1 g, signs of severe clinical toxicity were evident, and after only three doses, necropsies demonstrated severe bone marrow hypoplasia, cystitis, and intestinal necrosis. At all intravesical doses, significant systemic absorption was seen. The T1/2 (+/- SD) for intravesical and i.v. administration of 350 mg was 328 (+/-6.8) min and 99.3 (+/-5.2) min, respectively (P<0.001). Intravesical gemcitabine is well tolerated and has no direct bladder toxicity at doses up to 1000 mg/m2. Higher doses result in gastrointestinal, bladder, and bone marrow toxicity.

Absorption↗
PubMed1998

Risk assessment for metastatic testis cancer.

Metastatic germ cell tumors represent a model for curable malignancy, with 70% to 80% of patients cured of their disease. Patients with a good prognosis are likely to be cured, and the aim of investigation is to maintain the high cure rate while minimizing toxicity. For patients who fail to achieve a complete response (CR) to therapy, or who relapse after achieving CR, the prognosis is poor--these patients have become the focus of more intensive treatment to increase the cure rate. Distinguishing which patients will require more aggressive therapy ab initio has been the goal of successive attempts to stratify patients into either good- or poor-risk groups to tailor treatment accordingly. A number of analyses have yielded variable factors and differing schemas to classify patients, culminating in the International Germ Cell Consensus Group whose findings have been utilized to develop the new testicular cancer staging system for the American Joint Committee on Cancer (AJCC) and the Union International contre le Cancre (UICC). This article traces the developments in risk assessment that have lead to this consensus, which would prospectively allow comparison among future clinical trials.

Biomarkers, Tumor↗
PubMed1998

Poor-risk germ cell tumors. Recent developments.

Standard therapy for patients with poor-risk germ cell tumors remains four cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, which cures approximately 50% of this patient population. Randomized trials of conventional-dose chemotherapy have failed to identify a regimen with superior efficacy to BEP. Preliminary data suggesting efficacy for high-dose chemotherapy with stem cell or autologous bone marrow transplantation as initial therapy for poor-risk disease have led to two randomized trials of this approach as initial therapy for poor-risk patients. The recently developed International Germ Cell Consensus Classification provides a standard method for determining poor-risk status and should be uniformly applied for both clinical decision making and risk assignment in clinical trials.

Antineoplastic Agents↗
PubMed1998

New chemotherapy regimens for metastatic bladder cancer.

M-VAC remains the standard of care for metastatic transitional cell carcinoma (TCC), but its limitations include significant toxicity and infrequent durable disease-free survival. Recent investigation has focused on the identification of novel chemotherapeutics with single-agent activity in metastatic TCC and on their incorporation into more active combination regimens. Paclitaxel, gemcitabine and ifosfamide are among the most active new agents. Numerous phase II trials of novel combinations have yielded promising preliminary results. Longer follow-up and results from randomized trials will be necessary to determine the impact of newer chemotherapy regimens on survival.

Journal Article↗
PubMed1998

Metastatic germ cell tumors: modeling for response to chemotherapy.

PURPOSE: This study sought to determine factors that predict response to chemotherapy for patients with advanced germ cell tumors (GCTs), to evaluate different methods by which serum tumor markers can be used to predict response independent of assay method, and to develop criteria to guide allocation to clinical trials. METHODS: Pretreatment data from 796 patients treated with platinum-based chemotherapy on Memorial Hospital protocols from 1975 to 1990 were analyzed. Multivariate analyses were performed on a developmental data set (n = 597) to assess for independently significant predictors of response. Predictive models developed using these methods were confirmed on the validation set (n = 199). RESULTS: Independently significant factors for response included a mediastinal primary tumor (.015), pure seminomatous histology (.002), metastases to nonpulmonary visceral sites (bone, liver, and brain; .0001), and the pretreatment values of lactate dehydrogenase (LDH; .0001) and human chorionic gonadotropin (HCG; .0001). The likelihood of complete response (CR) was increased by seminomatous histology and decreased by the other factors. Serum levels of HCG and LDH could predict outcome independent of assay methodology. A model to predict good-, intermediate-, and poor-risk categories with CR rates of 92%, 76%, and 39%, respectively, was developed. CONCLUSION: The independent prognostic factors of serum tumor markers LDH and HCG, the sites of metastases, and the primary origin of GCTs can predict outcome in patients with advanced GCT. These factors should be considered in the allocation of patients with advanced disease to clinical trials and have been included in the new tumor-node-metastasis (TNM) staging systems developed for the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome.

PURPOSE: To evaluate the 10-year outcome of patients with invasive (T2-3N0M0, staged according to the tumor, node, metastasis system) bladder cancer who responded completely to a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by bladder-sparing surgery. PATIENTS AND METHODS: Of 111 surgical candidates who received neoadjuvant MVAC, 60 (54%) achieved a complete clinical response (T0) on transurethral resection (TUR) of the primary tumor site. Of these, 28 requested follow-up with TUR alone, 15 had a partial cystectomy, and 17 elected a radical cystectomy. The patients were followed up for a median of 10 years (range, 8 to 13 years). RESULTS: Of 43 patients who had bladder-sparing surgery, 32 (74%) are alive, which includes 25 (58%) with an intact functioning bladder. Twenty-four patients (56%) developed bladder tumor recurrences from 5 to 96 months, which were invasive in 13 (30%) and superficial in 11 (26%). Thirteen patients required a salvage cystectomy, of whom 6 died, which includes 4 (9%) from a new invasive neoplasm. Of the 17 patients who had radical cystectomy, 11 (65%) are alive. CONCLUSION: The majority of patients with invasive bladder tumors who achieve T0 status after neoadjuvant MVAC chemotherapy preserve their bladders for up to 10 years with bladder-sparing surgery. The bladder remains at risk for new invasive tumors. Cystectomy salvages the majority, but not all, of relapsing patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial.

PURPOSE: A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS: Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS: Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION: ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.

Adult↗
PubMed1998

Medical and surgical management of pulmonary metastases from germ cell tumors.

GCT is considered a curable tumor with a greater than 90% overall long-term survival. Pulmonary metastasis is common in patients with disseminated disease. First-line therapy in the management of patients with pulmonary metastases from germ cell tumors is cisplatin-based chemotherapy. Pulmonary metastasectomy has an important adjuvant role in a subset of patients who have residual radiographic abnormalities or progression of disease despite optimal chemotherapy. Surgical resection of residual pulmonary and mediastinal disease provides an accurate response assessment and consolidates the chemotherapy by removal of any viable GCT. Therefore, surgical resection of all residual masses is indicated in patients with NSGCT and normalized serum value of tumor markers after definitive systemic chemotherapy. Surgical resection or biopsy is a reasonable alternative in residual seminoma > or = 3 cm in diameter.

Antineoplastic Agents↗
PubMed1998

Therapy for good risk germ cell tumors.

Patients with good-prognosis germ cell tumors are those with the highest likelihood of cure. By identifying pre-treatment risk assignment, these patients may be treated with the most efficacious and least toxic regimens, while poor-risk patients may be selected to receive potentially more toxic combinations to optimize cure rates. The lack of uniform criteria of good-risk disease has been addressed by an international consortium, the International Germ Cell Cancer Collaborative Group. Recommendations for three risk strata, defined by serum tumor markers and specific sites of disease provide reproducible subsets of good-, intermediate-, and poor-risk populations that allow international trial collaborations and direct comparison of good-risk therapies and outcomes. Despite different criteria defining good-risk disease, trials in these patients have successfully eliminated bleomycin from combination regimens, have reduced the number of cycles of therapy, and have proven that carboplatin cannot replace cisplatin. As a consequence of controlled studies, three cycles of bleomycin, etoposide, and cisplatin (BEP) or four cycles of etoposide and cisplatin, using a 5-day etoposide schedule have been established as American standards. In Europe, four cycles of BEP using the 3-day etoposide schedule is considered the standard schedule. Because the schedule of etoposide is not uniform, prospective evaluation is necessary to determine whether the 3-day European standard is the equivalent of the 5-day American standard.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma.

PURPOSE: A phase II trial of docetaxel was conducted to assess its efficacy and toxicity in patients with advanced transitional-cell carcinoma (TCC) who had failed to respond to prior cisplatin-based therapy. PATIENTS AND METHODS: Thirty assessable patients who had failed to respond to or relapsed after one prior cisplatin-containing regimen were treated with docetaxel 100 mg/m2 over 1 hour, every 21 days. All patients were premedicated with dexamethasone and diphenhydramine to reduce allergic reactions. Reductions of subsequent doses were made for severe hematologic toxicity. Prophylactic hematopoietic growth factors were not used. RESULTS: Four of 30 patients (13.3%; 95% confidence interval [CI], 3.8% to 30.7%) demonstrated a partial response (PR), with durations of response ranging from 3 to 8 months. The estimated median survival duration for all patients is 9 months (95% CI, 6 to 12 months) with a median follow-up time of 14 months (range, 1 to 27). Hematologic toxicity included anemia, thrombocytopenia, neutropenia, and febrile neutropenia. Nonhematologic toxicity included alopecia and mucositis. Fluid retention was not observed and cutaneous toxicity was mild and infrequent. Dose reductions were necessary for adverse events in 18 patients (60%). CONCLUSION: Docetaxel is an active single agent in previously treated patients with TCC of the urothelial tract. Therapy was well tolerated in this patient population but myelosuppression was frequent. Further study in previously untreated patients, both alone and in combination, is warranted.

Adult↗
PubMed1997

Phase II randomized trial of gallium nitrate plus fluorouracil versus methotrexate, vinblastine, doxorubicin, and cisplatin in patients with advanced transitional-cell carcinoma.

PURPOSE: A phase II randomized trial of gallium nitrate/fluorouracil (5-FU) versus dose-intense methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was performed in poor-risk patients with advanced urothelial tract tumors. The efficacy and toxicity of these regimens were compared. Assessment of dose-intense M-VAC as salvage treatment in patients who failed to respond to the gallium nitrate/5-FU regimen was also performed. PATIENTS AND METHODS: Thirty-four patients who had not received prior systemic chemotherapy were randomized to either arm of the study. All patients had one or more clinical features predicting a low likelihood of durable complete response to standard chemotherapy, ie, weight loss, visceral metastases, and low performance status. Gallium nitrate and 5-FU were each administered by continuous 5-day infusions every 28 days. M-VAC was recycled every 21 days, with prophylactic recombinant human granulocyte colony-stimulating factor (rh-G-CSF). RESULTS: Two of 17 patients (12%; 95% confidence interval [CI], 1.4% to 36.4%) had a major response to gallium nitrate/5-FU. Sixteen of 17 patients treated with M-VAC (94%; 95% CI, 71.3% to 99.8%) demonstrated a major response. Five of 12 patients who failed to respond to the gallium nitrate/5-FU combination responded to M-VAC as second-line therapy (42%; 95% CI, 15.2% to 72.3%). Median survival for the gallium nitrate and 5-FU arm was 19 versus 17 months for the M-VAC arm, with a median follow-up duration of 35 months (range, 2 to 51) for all patients. Dose-intense M-VAC was associated with a greater incidence of neutropenia and thrombocytopenia. CONCLUSION: Dose-intense M-VAC is superior to gallium nitrate/5-FU in poor-risk patients (P < .0001). Despite the overall high response rate, the median survival for patients with M-VAC remained unsatisfactory. Similar survival distributions were observed for patients who received investigational therapy followed by cisplatin-based therapy and patients treated with initial cisplatin-based therapy.

Adult↗
PubMed1997

High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.

PURPOSE: A treatment program that included high-dose carboplatin, etoposide, and cyclophosphamide (CEC) followed by autologous bone marrow transplantation (AuBMT) was investigated as first-line therapy in patients with poor-risk germ cell tumors (GCTs). PATIENTS AND METHODS: Previously untreated GCT patients with poor-risk features were treated with etoposide, ifosfamide, and cisplatin (VIP) with or without high-dose CEC plus AuBMT. Patients qualified for a change to high-dose CEC if a prolonged clearance of elevated serum tumor markers was observed after two cycles of the cisplatin-containing regimen. RESULTS: Sixteen patients were treated with VIP alone and 14 with VIP and high-dose CEC. Seventeen patients (57%) achieved a complete response. Twenty are alive (67%) and 15 (50%) are free of disease at a median follow-up time of 30 months. For 23 cycles of high-dose CEC, the median time from AuBMT to a granulocyte count > or = 0.5/microL was 11 days (range, 0 to 14) and to a platelet count 50,000/microL, 19 days (range, 14 to 34). The survival of 58 patients treated in two of our center's programs that incorporated high-dose chemotherapy (high-dose carboplatin plus etoposide [CE] and CEC) was compared with our prior experience with conventional-dose cisplatin chemotherapy alone in poor-risk GCT. Patients treated with marker-dependent, early-intervention high-dose chemotherapy experienced longer survival (P = .001). CONCLUSION: In this setting, high-dose CEC was well tolerated, cumulative toxicity was lacking, and the recovery of blood counts after AuBMT was rapid. A randomized trial has been initiated to investigate further the role of high-dose CEC in first-line therapy for patients with poor-risk GCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.

PURPOSE: To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP). PATIENTS AND METHODS: Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported. RESULTS: One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years. CONCLUSION: Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.

Adolescent↗
PubMed1997

Ifosfamide- and cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: response and survival.

PURPOSE: To evaluate the efficacy and toxicity of ifosfamide- and cisplatin-containing chemotherapy as first-line salvage treatment for patients with germ cell tumors (GCT). PATIENTS AND METHODS: Fifty-six patients with advanced GCT resistant to one prior cisplatin-containing regimen were treated with a salvage chemotherapy regimen of ifosfamide, cisplatin, and either vinblastine or etoposide (VeIP/VIP). RESULTS: Twenty of 56 (36%) assessable patients achieved a complete response (CR). Thirteen (23%) are alive and continuously free of disease at a median follow-up time of 52 months; the median survival duration was 18 months. Among patients with a testis primary tumor site and a prior CR to first-line therapy, 65% are alive and 41% continuously disease-free, and the median survival time has not been reached. In contrast, for patients with an extragonadal primary tumor or with a testis primary tumor site and an incomplete response (IR) to first-line therapy, 31% are alive and 15% continuously free of disease, with a median survival time of 12 months (P < .03). CONCLUSION: Ifosfamide- and cisplatin-containing therapy achieves a durable CR in a minority of patients with resistant GCT as first-line therapy. Patients with a primary testis site who relapsed from a CR to first-line cisplatin therapy have a better prognosis than patients with an extragonadal primary tumor site or an IR to first-line therapy. Risk-directed clinical trials to improve response and survival in both subsets are warranted.

Adolescent↗