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J D Bitran

Publications and source records attributed to J D Bitran.

At least 19 recordsLinked to original sources
PubMed2000

Delphi-panel analysis of appropriateness of high-dose chemotherapy and blood cell or bone marrow autotransplants in women with breast cancer.

BACKGROUND: There is controversy whether high-dose chemotherapy and a blood cell or bone marrow autotransplant is a better treatment than conventional-dose chemotherapy for women with local/regional or metastatic breast cancer. Subject selection and time-to-treatment biases make definitive comparison impossible. Recent results of randomized trials are contradictory. OBJECTIVE: Determine appropriateness of high-dose chemotherapy and a blood cell or bone marrow autotransplant in women with breast cancer. PANELISTS: Nine breast cancer experts from diverse geographic sites and practice settings. EVIDENCE: Boolean MEDLINE searches of 'breast cancer' and 'chemotherapy' and/or 'blood cell' or 'bone marrow transplants'. PROCESS: We used a modified Delphi-panel group judgement process. Clinical variables were permuted to define 2058 clinical settings. Each panelist rated appropriateness of high-dose therapy and an autotransplant versus conventional therapy on a 9-point ordinal scale (1: most inappropriate, 9: most appropriate). An appropriateness index was developed based on median rating and amount of disagreement. The relationship of appropriateness indices to the permuted clinical variables was considered by analysis of variance and recursive partitioning. CONCLUSIONS: In women with local/regional breast cancer autotransplants were rated: 1) appropriate in those with > or = 10 cancer-involved lymph nodes; 2) uncertain in those with 4-9 cancer-involved nodes; and 3) inappropriate in women with < or = 3 cancer-involved lymph nodes. In women with metastatic breast cancer autotransplants were rated: 1) appropriate in those with metastases to 'favorable' sites (skin, lymph node, pleura) and a complete or partial response to chemotherapy; 2) uncertain in women with metastases to 'unfavorable' sites (lung, liver, or central nervous system) and a complete response to chemotherapy or those with bone metastases and a complete or partial response or stable disease after chemotherapy; and 3) inappropriate in other settings.

Antineoplastic Agents↗
PubMed2000

Transplantation of CD34+ peripheral blood cells selected using a fully automated immunomagnetic system in patients with high-risk breast cancer: results of a prospective randomized multicenter clinical trial.

Tumor contamination of autologous peripheral blood stem/progenitor cell grafts occurs in a substantial proportion of high-risk breast cancer patients, and the possibility that such contamination may contribute to relapse has focused attention on methods for removal of the contaminating cells prior to transplantation. One such approach is positive selection of CD34+ cells. A fully automated immunomagnetic cell selection system has recently been introduced to facilitate the positive selection process. A multicenter randomized clinical trial was designed to evaluate the capacity of CD34+ cells isolated using the fully automated system to support prompt hematopoietic reconstitution following high-dose chemotherapy in high-risk breast cancer patients, as well as to assess the safety and tolerability of the CD34+ cell transplants. In recipients of isolated CD34+ cells, the median time to an absolute neutrophil count > or =500/microl was 10 days, a value identical to that observed in patients receiving unfractionated apheresis collections. In the isolated CD34+ cell recipients median time to a platelet count > or =20 000/microl was 12 days, compared with 10 days in the unfractionated cell group. There were no statistically significant differences between the groups in median time to neutrophil or platelet engraftment. Infusion of autologous cells was well tolerated by the study groups. There were no inter-group differences in the incidence of infections, need for platelet transfusions, or duration of hospitalization. Isolated CD34+ cells were high in purity and sufficient in number for use in autologous transplantation. The fully automated immunomagnetic cell selection system affords an efficient and time-saving option for isolation of CD34+cells to be used as autologous grafts in high-risk breast cancer patients, and the isolated CD34+ cells support undelayed hematopoietic reconstitution.

Adult↗
PubMed1999

Factors correlated with progression-free survival after high-dose chemotherapy and hematopoietic stem cell transplantation for metastatic breast cancer.

CONTEXT: Women with breast cancer are the most frequent recipients of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autotransplants) in North America. Despite widespread use, controversy exists about the benefits of and appropriate patients for this therapy. OBJECTIVE: To determine factors associated with disease progression or death after autotransplantation in women with metastatic breast cancer. DESIGN: Analysis of data collected retrospectively (January 1989 to 1992) and prospectively (1992 through January 1995) for the Autologous Blood and Marrow Transplant Registry. SETTING: Sixty-three hospitals in North America, Brazil, and Russia. PARTICIPANTS: A total of 1188 consecutive women aged 18 to 70 years receiving autotransplants for metastatic or locally recurrent breast cancer, with a median follow-up of 291/2 months. MAIN OUTCOME MEASURE: Time to treatment failure (disease progression, disease recurrence, or death) after autotransplantation. RESULTS: Factors associated with significantly (P<.05) increased risk of treatment failure in a Cox multivariate analysis included age older than 45 years (relative hazard, 1.17; 95% confidence interval [CI], 1.02-1.33), Karnofsky performance score less than 90% (1.27; 95% CI, 1.07-1.51), absence of hormone receptors (1.31; 95% CI, 1.15-1.51), prior use of adjuvant chemotherapy (1.31; 95% CI, 1.10-1.56), initial disease-free survival interval after adjuvant treatment of no more than 18 months (1.99; 95% CI, 1.62-2.43), metastases in the liver (1.47; 95% CI, 1.20-1.80) or central nervous system (1.56; 95% CI, 0.99-2.46 [approaches significance]) vs soft tissue, bone, or lung, 3 or more sites of metastatic disease (1.32; 95% CI, 1.13-1.54), and incomplete response vs complete response to standard-dose chemotherapy (1.65; 95% CI, 1.36-1.99). Receiving tamoxifen posttransplantation was associated with a reduced risk of treatment failure in women with hormone receptor-positive tumors (relative hazard, 0.60; 95% CI, 0.47-0.87). Women with no risk factors (n = 38) had a 3-year probability of progression-free survival of 43% (95% CI, 27%-61 %) vs 4% (95% CI, 2%-8%) for women with more than 3 risk factors (n = 343). CONCLUSION: These data indicate that some women are unlikely to benefit from autotransplantation and should receive this treatment only after being provided with prognostic information and in the context of clinical trials attempting to improve outcome.

Adult↗
PubMed1998

High-dose chemotherapy consolidation with autologous stem cell rescue in metastatic breast cancer: a 10-year experience.

One hundred women with metastatic breast cancer (MBC) underwent high-dose chemotherapy with autologous stem cell rescue at our institution beginning in 1986. The patients underwent induction chemotherapy from June 1986 to December 1993. Patients who showed stable or responsive disease underwent HDC with cyclophosphamide (CY) at 7.5 g/m2 and thiotepa (TPA) at 675 mg/m2 or the same doses of CY and TPA with carmustine at 450 mg/m2. The source of stem cell rescue was either BM alone, BM and G-CSF-mobilized peripheral blood progenitor cells (PBPC) or PBPC alone if patients had BM involvement with MBC. With a median follow-up of 62 months (range 1-109 months), median survival from reinfusion was 16 months with a 5-year survival of 19+/-4%. The median event-free survival (EFS) was 8 months with a 5-year EFS of 11+/-3%. Patients achieving a complete response to induction therapy showed a higher 5-year EFS from reinfusion of 31+/-8% in contrast to 3+/-3% (P = 0.006) for patients who achieved a partial response to induction therapy prior to HDC. Marrow involvement or source of stem cell rescue did not affect outcome. Our mature results confirm that high-dose chemotherapy with autologous stem cell rescue can confer a prolonged DFS in a subset of women with MBC. However, the high rate of relapse remains a universally disturbing problem in this patient population.

Adult↗
PubMed1998

Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating factor support in stage IV breast cancer.

PURPOSE: This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topotecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity. PATIENTS AND METHODS: Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3 hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to 5. Patients received an abbreviated premedication regimen that consisted of ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d subcutaneously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan concentrations were assessed during the first cycle using limited-sampling strategies. RESULTS: Seventeen patients were treated. The majority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and maximum concentration (Cmax) of paclitaxel. CONCLUSION: This regimen does not produce a response rate superior to that expected with single-agent paclitaxel at doses that do not require growth factor support.

Adenocarcinoma↗
PubMed1996

Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer.

The aim of this phase II study was to determine the feasibility of using two (tandem) courses of high-dose alkylating agents with bone marrow or peripheral blood progenitor cell support in women with stage IV breast cancer. Women with stage IV breast cancer who had achieved a CR or PR during conventional chemotherapy were enrolled in a phase II trial of high-dose cyclophosphamide 7500 mg/m2 and thiotepa 675 mg/m2 (C+T) followed within 180 days by high-dose melphalan (M) 140 mg/m2. Bone marrow and/or GM-CSF mobilized peripheral blood hematopoietic progenitor cells were used to support high-dose C+T and high-dose M. Twenty-seven women were enrolled in this trial. The median age was 45 years (range 32-56). The median PS was 0 and all patients had achieved either a CR (4/27, 15%) or PR (23/27, 85%) to conventional chemotherapy. All 27 women underwent high dose C+T. The predominant toxicities were mucositis (81%), and diarrhea (81%); two patients (7%) died from infectious complications. Following C+T, the median time to hematologic recovery for neutrophils (ANC > 500 cells/mu 1) was 12 days and for platelets (>20 000 cell/mu 1), 23 days. Following C+T, 18 of 22 patients received high dose M; the predominant toxicities were nausea, vomiting (70%), and mucositis (91%). The median time to hematologic recovery for the ANC was 13 days and for platelets, 18 days. The overall response after high dose C+T and high dose M was 67% (CR, 15/27 patients (56%) and PR* (complete resolution of all measurable disease but persistent lytic disease or positive bone scan) 3/27 patients (11%). With median follow-up of 24 months, the actuarial freedom from relapse or treatment failure is 56% at 24 months. At 30 months 56% of patients are alive. For patients who achieve a CR or PR* the actuarial freedom from relapse or treatment failure at 24 months is 88%. In women with stage IV breast cancer who attain a CR or PR to conventional chemotherapy, tandem high-dose chemotherapy with ABMT can lead to prolonged relapse-free survival.

Adult↗
PubMed1996

A phase II study of cyclophosphamide followed by PIXY321 as a means of mobilizing peripheral blood hematopoietic progenitor cells.

Fourteen patients with stage II-IV breast cancer were enrolled in a phase II study of cyclophosphamide followed by PIXY321 as a means of mobilizing peripheral blood progenitor cells (PBPC). All 14 women tolerated PIXY321 well, with the predominant toxicities being erythema at the injection site, fever, and arthralgias. A median of two aphereses yielded a mean of 1.3 x 10(8) mononuclear cells/kg, 8.9 x 10(4) colony-forming units-granulocyte/macrophage (CFU-GM)/kg, and 4.5 x 10(6) CD34+ cells/kg. All 14 patients underwent high-dose chemotherapy with PBPC support, the median day to ANC >500 cells/microliter was 10.6, and the median day to platelets >20,000 cells/microliter was 13. The day of 90th percentile platelet recovery was 15. When compared to PBPCs mobilized by cyclophosphamide followed by GM-CSF, the use of PIXY321 may confer an advantage of enhanced platelet recovery.

Adult↗
PubMed1996

Her2/neu overexpression is associated with treatment failure in women with high-risk stage II and stage IIIA breast cancer (>10 involved lymph nodes) treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support following standard-dose adjuvant chemotherapy.

Twenty-five patients with high-risk stage II and IIIA breast cancer (>10 or more involved lymph nodes) were treated with six cycles of standard-dose chemotherapy (5-fluorouracil, doxorubicin, and cyclophosphamide) followed by high-dose chemotherapy (2.5 g/m2 cyclophosphamide for 3 days and 225 mg/m2 thiotepa for 3 days) with autologous hematopoietic progenitor cell support. The actuarial relapse free survival at 3 years is 80%; the actuarial survival at 3 years is 96%. Four patients relapsed systemically between 6 and 18 months; all four patients who relapsed had breast cancers that overexpressed Her2/neu. In contrast, none of the 21 patients who had no or borderline overexpression of Her2/neu relapsed (P = 0.00004, Fisher's exact test). Patients with high-risk stage II and IIIA breast cancer who have overexpression of Her2/neu appear to be at a high risk for relapse, even when treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support.

Adult↗
PubMed1995

A phase II study of recombinant interferon-gamma following combination chemotherapy for patients with extensive small cell lung cancer. CALGB.

A total of 71 patients with extensive small cell lung cancer were enrolled in CALGB study 8733. Chemotherapy was administered with cisplatin 33 mg/m2, i.v. infusion days 1-3, doxorubicin 45 mg/m2 i.v. day 1, cyclophosphamide 800 mg/m2 i.v. day 1, and etoposide 80 mg/m2 i.v. infusion days 1-3 (PACE). Following four courses of PACE, patients achieving a CR or PR were started on recombinant interferon-gamma (rINF-gamma) 0.2 mg s.c. daily until grade IV toxicities or progression occurred. Of the 71 patients enrolled, 67 are evaluated (47 males and 20 females), median age 59 years, and median PS1. The response rate to PACE was 48/67, 72%. Grade 3-4 toxicities included granulocytopenia, thrombocytopenia, and five treatment-related deaths (7%). Forty-one patients were started on rINF-gamma. Of these 41 patients, 11 were in CR, 30 in PR. The objective response rate to rINF-gamma was 2/30 or 6.7%. Recombinant rINF-gamma is inactive in small cell lung cancer, even when the tumor burden has been substantially reduced by prior chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

High-dose intravenous melphalan: a review.

PURPOSE: To review the clinical pharmacology and clinical trials that have used intravenous (IV) high-dose melphalan (HDM). METHODS: We reviewed the mechanism of action, clinical pharmacology, and clinical studies of HDM with and without autologous bone marrow support (ABMT) or peripheral-blood progenitor cells (PBPCs) in the following disease areas: myeloma, ovarian cancer, malignant lymphoma, breast cancer, neuroblastoma, Ewing's sarcoma, and acute leukemia. RESULTS: HDM has a distribution half-life (t1/2 alpha) of 5 to 15 minutes and an elimination half-life (t1/2 beta) of 17 to 75 minutes at doses of 140 to 180 mg/m2, with significant intrapatient variability. At these doses, a wide range of areas under the concentration/time curve (AUC) have been reported, ie, 146 to 1,515 mg/min/mL. HDM has significant clinical activity in patients with multiple myeloma in relapse or when used as consolidative therapy in relapsed ovarian cancer, relapsed Hodgkin's disease, breast cancer, and relapsed neuroblastoma. Additional studies are required to determine the activity of HDM in Ewing's sarcoma or acute leukemia. Toxicities of HDM include myelosuppression, moderate nausea and vomiting, moderate to severe mucositis and diarrhea, and, infrequently, hepatic venoocclusive disease. CONCLUSION: HDM has become an established and effective salvage regimen for children with relapsed neuroblastoma, as well as an effective consolidative treatment for children with high-risk disease (stage IV). HDM is emerging as an active and effective mode of treatment in patients with stage II and III myeloma. The favorable toxicity profile of HDM and the availability of PBPCs allows for repetitive therapy.

Acute Disease↗
PubMed1995

Dose intensification--a phase I study of ifosfamide with vinorelbine (Navelbine): rationale and study design in advanced non-small cell lung cancer.

A phase I trial of a combination of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) and ifosfamide given on a novel schedule on 3 consecutive days with granulocyte colony-stimulating factor was conducted to establish the maximum tolerated dose of vinorelbine and the dose-limiting toxicities of this regimen. Doses of vinorelbine were escalated in cohorts of patients. Of the 29 patients enrolled at the time of data analysis, 26 were evaluable for toxicity. At the first dose level (ifosfamide 2.0 g/m2 days 1, 2, and 3; vinorelbine 15 mg/m2 days 1, 2, and 3), two of three patients had dose-limiting toxicities. The dose of ifosfamide was decreased by 20%, and dose escalation of vinorelbine was restarted. At the vinorelbine dose level of 35 mg/m2/d for 3 days, three of four patients had dose-limiting toxicities. The recommended phase II doses were established as 1.6 g/m2/d ifosfamide for 3 days and 30 mg/m2/d vinorelbine for 3 days. This study established that granulocyte colony-stimulating factor was needed for approximately 8 days. We are currently examining the feasibility of two dose levels of vinorelbine (25 mg/m2 and 30 mg/m2/d for 3 days) in combination with ifosfamide (1.6 g/m2/d) given every 2 weeks.

Adult↗
PubMed1995

Paclitaxel and ifosfamide: a multicenter phase I study in advanced non-small cell lung cancer.

Both paclitaxel and ifosfamide have significant single-agent activity in non-small cell lung cancer. We designed a phase I study combining escalating doses of paclitaxel, administered by 24-hour infusion, with ifosfamide given at a dose of 1.6 g/m2 daily x 3. Paclitaxel dose levels were 135, 170, 200, 250, and 300 mg/m2. The goal of the study was to determine the maximum tolerated dose and dose-limiting toxicities of paclitaxel when used in this combination. Dose escalation was possible because of the use of filgrastim, a granulocyte colony-stimulating factor. Twenty-five patients at three institutions were treated. The dose-limiting toxicity of the combination was granulocytopenia, with other toxicities being generally mild to moderate. The maximum tolerated dose of paclitaxel was 300 mg/m2, and the recommended phase II dose is 250 mg/m2. There was a suggestion of a dose-response curve with paclitaxel as all three partial responses were seen at the 250 mg/m2 dose level. An additional II patients had objective regression or stable disease lasting for 9 to 30 weeks. A phase II study of this combination is currently being planned by the Cancer and Leukemia Group B.

Adult↗
PubMed1995

Acute myeloid leukemia and myelodysplasia following intensive chemotherapy for breast cancer.

Two major classes of therapy-related acute myeloid leukemias (t-AML) and myelodysplastic syndromes (t-MDS) have been described following the use of conventional doses of alkylating agents and epipodophyllotoxins. They are characterized by distinct clinical presentations and chromosomal abnormalities. We report 2 cases of t-AML and 1 case of t-MDS in 3 out of 36 women who underwent high-dose chemotherapy and attempted ABMT for breast cancer. Two patients developed t-AML 4 and 8 months following the initiation of high-dose chemotherapy with or without ABMT. The third patient developed t-MDS 23 months following dose-intensive chemotherapy and ABMT. Cytogenetic studies of the marrow metaphase chromosomes from the two patients who developed t-AML, including FISH analysis in 1 patient, showed a t(9;11)(p22ng,q23) abnormal chromosome 6 (ring chromosome). Neither patient had a preleukemic phase. Cytogenetic studies from the third patient who developed t-MDS showed abnormalities of chromosome 5 (-5) and a derivative of chromosome 17. The use of multiple chemotherapeutic agents in all 3 patients makes it difficult to attribute the development of these cases of t-MDS/t-AML to a single chemotherapeutic agent. The possible role of dose-intensive chemotherapy in the development of these secondary malignancies is discussed.

Acute Disease↗
PubMed1995

A phase I study of ifosfamide and doxorubicin with recombinant human granulocyte colony-stimulating factor in stage IV breast cancer.

Our objective was to define the maximum tolerated dose of an escalating dose of ifosfamide in combination with a fixed dose of doxorubicin supported by granulocyte colony-stimulating factor (Neupogen). Eighteen women with stage IV breast cancer were enrolled in a Phase I study of an escalating dose of ifosfamide (1.2 g/m2/day for 5 days-2.75 g/m2/day for 5 days) with doxorubicin 20 mg/m2/day for 3 days. Granulocyte colony-stimulating factor was used at 5 microgram/kg on day 6 until hematological recovery. Prophylactic antibiotics were also used. The maximum tolerated dose of ifosfamide in combination with doxorubicin was 2.75 g/m2/day for 5 days. The objective response rate was 83% with a complete response rate of 33% (6/18 patients); the median time to treatment failure was 11.5 months. The median survival has not been reached and will exceed 18 months. We concluded that the recommended dose of ifosfamide in combination with doxorubicin is 2.5 g/m2/day for 5 days. This combination shows promise in stage IV breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗