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J D Bitran

Publications and source records attributed to J D Bitran.

At least 37 records · Page 2Linked to original sources
PubMed1990

A phase I-II study of high-dose cyclophosphamide, thiotepa and escalating doses of mitoxantrone with autologous stem cell rescue in patients with refractory malignancies.

Twenty-five patients with refractory solid tumors were treated with high-dose cyclophosphamide, thiotepa and mitoxantrone followed by autologous stem cell rescue in a phase I dose escalation study. The dose-limiting toxic effect was mucositis at 60 mg/m2 of mitoxantrone in combination with cyclophosphamide and thiotepa. The early death rate due to toxic effects was 24%; all deaths were attributed to infections. Hematopoietic recovery was quite prolonged with median times to granulocyte (greater than 500 x 10(6)/l) and platelet (greater than 50 x 10(9)/l) recovery at 58 and 148 days, respectively. The overall response rate was 56%. The median time to progression was 14 weeks. Thus, this regimen has activity against refractory malignancies although early and prohibitive toxicity occurs when mitoxantrone is escalated in this setting.

Actuarial Analysis↗
PubMed1990

Patients at increased risk for late engraftment after transplantation: a novel method for their identification.

The time to platelet engraftment (platelets greater than 50 x 10(9)/l for 3 successive days without transfusions) is a major endpoint in treatment regimens of high dose chemotherapy and autologous stem cell rescue. A number of transplanted patients die before recovery of platelets. To include such patients appropriately in an analysis to identify prognostic factors for engraftment, a proportional odds model was employed. The outcome measure was a categorization of patients into four levels based on time to engraftment: early (0-40 days), intermediate (41-70 days), late (greater than 70 days) or died without engraftment. Of 45 women with advanced breast cancer who underwent high dose chemotherapy and autologous transplantation, there were: 10 early, 11 intermediate and eight late engrafters and 16 who died before platelet engraftment. Based on the proportional odds model applied to these data, four significant and independent prognostic factors for later or non-engraftment were revealed: lower numbers of mononuclear cells/kg harvested (p = 0.002), lower serum albumin level (p = 0.003), prior cisplatin chemotherapy (p = 0.006), and the existence of bone marrow malignancy (p = 0.025).

Adult↗
PubMed1989

Plasma pharmacokinetics of high-dose oral melphalan in patients treated with trialkylator chemotherapy and autologous bone marrow reinfusion.

The pharmacokinetics of melphalan following high-dose p.o. administration were determined in 17 patients with various malignancies for the purpose of assessing interpatient and intrapatient pharmacokinetic variability. All patients underwent bone marrow harvest on day -8 (relative to bone marrow reinfusion). On days -7, -6, and -5, melphalan was given p.o. and the dose was escalated on each cohort consisting of at least 3 patients (beginning at 0.75 mg/kg). On days -6, -4, and -2, cyclophosphamide at 2.5 g/m2 and thiotepa at 225 mg/m2 were given i.v. On day -7 the peak melphalan concentration was 1.64 +/- 0.89 (SD) microM with a terminal half-life of 1.56 +/- 0.86 h. The area under the plasma concentration time curve (AUC) and oral clearance were 217.9 +/- 115.1 microM/min and 30.2 +/- 14.2 ml/min/kg. There was only a moderate correlation between the melphalan dose and both the peak concentration (r = 0.50, P less than 0.05) and AUC (r = 0.64, P less than 0.01) over the dosage range of 0.75-2.5 mg/kg. There was a trend towards greater interpatient variability in peak concentration, AUC, and oral clearance observed at the higher doses of melphalan. Analysis of intrapatient pharmacokinetic variability in 8 patients showed a significant difference between the doses given on days -7 and -5 in the peak concentration (2.09 versus 1.07 microM, P = 0.02), AUC (264.9 versus 134.8 microM/min, P = 0.01), and oral clearance (25.1 versus 53.1 ml/min/kg, P = 0.05) but no significant difference in the time to peak and terminal half-life. We conclude that there is marked interpatient and intrapatient variability in melphalan pharmacokinetics following high-dose p.o. administration. The data are consistent with saturable absorptive pathways for melphalan, which might be especially sensitive to concurrent high-dose chemotherapy.

Absorption↗
PubMed1989

High-dose, multiple-alkylator chemotherapy with autologous bone marrow reinfusion in patients with advanced non-small cell lung cancer.

Fifteen patients with Stage IV lung cancer both untreated and previously treated were enrolled into a high-dose chemotherapy program with multiple alkylating agents and autologous bone marrow reinfusion. Eight patients received cyclophosphamide at 7.5 gm/m2 over 3 days with thiotepa escalated from levels of 1.8 mg/kg to 6.0 mg/kg over 3 days. Seven patients received the above dose of cyclophosphamide plus thiotepa at 675 mg/m2 and oral melphalan escalated from levels of 0.75 mg/kg to 2.5 mg/kg over 3 days. Both regimens are part of larger Phase I-II clinical studies. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets per microliter was 16 and 27 days, respectively. Two patients died as a consequence of severe, overwhelming infections during their period of aplasia. Of the 13 evaluable patients, no patients achieved a complete response and seven patients (47%) obtained a partial response. The median duration of response was 12 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, mucositis, skin rash, hemorrhagic cystitis, and cardiomyopathy. Since there are substantial toxicities associated with high-dose chemotherapy and responses of such brief duration, further investigation with these drug combinations is not warranted.

Adult↗
PubMed1989

The patterns of failure in patients with pathological stage I and II diffuse histiocytic lymphoma treated with radiation therapy alone.

Radiation therapy was used to treat 36 patients with pathological Stage I and II diffuse histiocytic lymphoma at The University of Chicago Hospitals from 1970 to 1986. Twenty-two patients had pathological Stage I and 14 had pathological Stage II diffuse histiocytic lymphoma. The patients were treated with a median tumor dose of 50 Gy (range of 40-60 Gy). Therapy consisted of extended field radiation therapy in 27 patients (extended mantle or total nodal irradiation) and involved field irradiation in nine patients. The 10-year actuarial relapse-free survival for pathological Stage I and pathological Stage II patients was 91% and 35%, respectively (median follow-up of 7 years). None of the 22 pathological Stage I patients had bulky mediastinal or abdominal disease. Of the 22 pathological Stage I patients, one failed in an unirradiated contiguous lymph node and one relapsed with disseminated disease. Of the 14 pathological Stage II patients, two patients with bulky disease failed in field, one patient failed in a contiguous node, three patients failed within the abdomen, and three patients failed with disseminated disease. To better evaluate the efficacy of staging laparotomy, we analyzed the patterns of failure of 17 clinical Stage I and II diffuse histiocytic lymphoma patients. Four of these patients failed in field (three in sites of bulky disease), and five patients relapsed in the abdomen (three with disseminated disease). Salvage treatment with multiagent chemotherapy resulted in second complete responses in seven of ten patients; however, all but one have recurred and are dead of disease. Radiation therapy may be used as the sole treatment in patients with pathological Stage I diffuse histiocytic lymphoma without bulky disease. Patients with pathological Stage II diffuse histiocytic lymphoma and clinically staged patients have a higher incidence of dissemination and relapse within the abdomen. A benefit resulting from the administration of extended field irradiation was not revealed by this study.

Adolescent↗
PubMed1989

High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer.

We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Neoadjuvant vindesine, etoposide, and cisplatin for locally advanced non-small cell lung cancer. Final report of a phase 2 study.

We treated 27 patients with regionally advanced non-small-cell lung cancer (NSCLC) with two cycles of neoadjuvant chemotherapy with etoposide, vindesine, and cisplatin. Twenty-three patients were evaluable for response; 13 had a partial response while ten patients had stable disease or disease progression. Subsequent local therapy consisted of surgery followed by radiotherapy in four patients and of radiotherapy alone in 14 patients. Five patients did not receive local therapy. At completion of local therapy, seven patients were considered free of disease including all four who had undergone surgery. Median time to disease progression for the 13 patients who had a partial response to neoadjuvant chemotherapy was eight months (three to 51+ months). The median survival for all patients registered on study was eight months (three days to 53+ months). Chemotherapy induced toxicities included moderate myelosuppression, nausea and vomiting in all patients, and occasional ototoxicity, neurotoxicity, and wasting syndrome. One patient died of intracerebral hemorrhage due to thrombocytopenia. This trial shows that administration of neoadjuvant chemotherapy to patients with locoregionally advanced NSCLC is feasible and may yield an increased response rate compared to patients with stage IV disease. While no clearly beneficial effect of the use of chemotherapy on patient survival is apparent in this study, further studies utilizing neoadjuvant chemotherapy in patients with NSCLC are warranted and should attempt to identify more active combinations of drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

High dose chemotherapy with autologous hematopoietic stem cell support in the treatment of refractory stage IV breast carcinoma.

Fourteen patients with refractory metastatic breast cancer were treated with high dose chemotherapy and autologous hematopoietic stem cell rescue. All patients received cyclophosphamide (7.5 g/m2 over 3 days) and thiotepa (150-225 mg/m2 over 3 days), three patients in addition received melphalan (4.5 mg/kg), and seven patients received carmustine (150-562 mg/m2). Toxicities included pancytopenia, infection, hemorrhagic cystitis, skin rash, nausea, vomiting, diarrhea, and mucositis. There was one toxic death secondary to sepsis and ventricular tachycardia. The overall response rate was 77% including a 15% complete response rate. The overall median survival for all patients was 6.0 months (range 2-22 months). The median survival for nonresponders was 3.5 months. The median duration of response was 89 days (range 40-262). In our experience high dose chemotherapy with autologous stem cell reinfusion produces a high response rate in refractory breast cancer. However, because of the short duration of response and overall survival, we feel this type of therapy should be utilized earlier in the course of disease.

Adult↗
PubMed1989

The role of high-dose therapy and autologous bone marrow reinfusion in the treatment of Hodgkin's disease.

In a significant fraction of patients with Hodgkin's disease, a condition develops that is resistant to conventional chemotherapy. Experience using high-dose chemotherapy, with or without TBI, and ABMR is expanding. In Hodgkin's disease, remissions can be achieved in approximately half of the patients with relapsed advanced disease. High-dose chemoradiotherapy regimens are toxic and require extensive supportive care. Relapse frequently occurs in areas of previous disease, which suggests failure of the conditioning regimen rather than infusion of occult tumor cells in the autologous bone marrow. Thus, the role of marrow purging in this therapy needs to be evaluated further. It is also important to evaluate the effects of more vigorous attempts at cytoreduction of bulky disease prior to high-dose therapy and ABMR. We recommend that high-dose therapy and ABMR in an investigational setting be used in patients with Hodgkin's disease who experience relapse after MOPP and ABVD or equivalent regimens. Toxicity can be decreased and efficacy increased only if therapy is administered to patients who have not been heavily pretreated and who have lower tumor burden and a good performance status. Finally, high-dose therapy with ABMR has a definite role in salvaging patients with refractory Hodgkin's disease. Many issues need to be resolved, including the optimal timing of this approach and the optimal conditioning regimen. In the years to come these questions may be answered by the many studies now under way.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung.

Combination chemotherapy is frequently used in the therapy of advanced non-small-cell lung cancer (NSCLC), but late complications are rarely recognized because of the short survival of most patients. Of 119 patients with advanced NSCLC treated with cisplatin and other drugs, four patients developed acute nonlymphocytic leukemia (ANLL). All four patients received etoposide and cisplatin with or without vindesine. Leukemia was diagnosed at 13, 19, 28, and 35 months after start of treatment. Three patients had morphologic and/or cytogenetic features of acute leukemia with significant monoblastic involvement; the fourth patient had trilineage dysplasia and cytogenetic abnormalities more commonly associated with therapy-related leukemia. Detailed analysis of the subgroup who survived longer than 1 year (24 patients) suggests that high cumulative doses of etoposide are leukemogenic; the median etoposide dose was 6,795 mg/m2 (first year only) in the four leukemic patients compared with 3,025 mg/m2 in the 20 nonleukemic patients (P less than .01). The rate of ANLL was 0.30 per person-year after the first year (95% confidence limits 0.11 to 0.90), with a cumulative risk of 15% +/- 11% at 2 years, and 44% +/- 24% at 2.5 years. We conclude that high doses of etoposide are potentially leukemogenic, and can induce a syndrome with features of acute monoblastic leukemia de novo that is distinct from other secondary leukemias.

Acute Disease↗
PubMed1985

Intraperitoneal bleomycin. Pharmacokinetics and results of a phase II trial.

Bleomycin was administered in a phase II trial to 10 patients with malignant ascites. Complete responses to intraperitoneal bleomycin were observed in 6/10 patients (60%). Pharmacokinetics of serum and intraperitoneal bleomycin showed peak levels at 15 minutes with a peritoneal fluid half-life of 4.2 +/- 0.1 hours and a serum half-life of 5.0 +/- 1.2 hours. There was a 400-fold difference in concentration when bleomycin was administered intra-abdominally. Toxicities with intraperitoneal bleomycin were minimal. This phase II trial confirms the efficacy of intraperitoneal bleomycin; further trials appear warranted.

Abdominal Neoplasms↗
PubMed1985

A phase II trial of cyclophosphamide and adriamycin in refractory squamous cell carcinoma of the head and neck. An effective salvage regimen.

A phase II trial of cyclophosphamide and adriamycin was carried out in 26 patients with recurrent squamous cell carcinoma of the head and neck, previously treated with cis-diamminedichloroplatinum-based regimens. The overall response rate was 46% (12/26 patients) with the median duration of response being 6.5 months. Cyclophosphamide and adriamycin is an active combination in patients with previously treated squamous cell carcinoma of the head and neck.

Adult↗
PubMed1979

The role of gallium-67 scanning in the clinical staging and preoperative evaluation of patients with carcinoma of the lung.

Gallium-67 scanning was evaluated in 100 patients with proved carcinoma of the lung. It was valuable in separating primary from secondary lung tumors, determining the extent of contralateral hilar or mediastinal lymph node involvement, and detecting distant organ metastases. In addition to multiplane whole-body Ga-67 tomographic scanning, colloid liver scans, bone scans, and computerized axial tomography scans of the brain were obtained to determine the presence of distant metastasis. The gallium scan detected 11 of 12 occult metastases and identified 7 of 7 liver, 9 of 14 brain, 4 of 4 soft tissues, 1 of 4 contralateral lung, and 9 of 11 bone metastases. The whole-body gallium scan accurately detected or excluded extrathoracic metastatic disease in 11 of 12 patients examined postmortem within three months of a gallium scan. An approach is recommended using gallium scanning along with chest roentgenograms for clinical staging and preoperative evaluation of patients with carcinoma of the lung. Specific organ scans should be reserved for the occasional symptomatic patient with a negative gallium scan or for clarification of an indeterminate gallium scan.

Bone Neoplasms↗
PubMed1978

Metastatic non-oat-cell bronchogenic carcinoma. Therapy with cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP).

Fifty-four patients with metastatic non-oat-cell bronchogenic carcinoma were treated with cyclophosphamide, doxorubicin hydrochloride (Adriamycin), methotrexate, and procarbazine hydrochloride (CAMP). Eighteen of 51 of these patients with measurable disease showed an objective response to CAMP chemotherapy, with a median survival of 12.6 months. Eight of the 18 patients are still alive, and two have been in continuous remission for 20 and 26 months. Survival for patients with stable disease was 12 months, similar to that for patients demonstrating objective regression in response to CAMP treatment. Weight loss, performance status, and dominant site of metastases proved to be important prognostic factors. The CAMP regimen was well tolerated; there were only two drug-related deaths, both secondary to infectious complications.

Adenocarcinoma↗