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Biomedical subjects

L A Kalish

Publications and source records attributed to L A Kalish.

At least 19 recordsLinked to original sources
PubMed1995

Ciprofloxacin versus trimethoprim/sulfamethoxazole for prophylaxis of bacterial infections in bone marrow transplant recipients: a randomized, controlled trial.

PURPOSE: To compare the efficacy and safety of ciprofloxacin (CIP) and trimethoprim/sulfamethoxazole (TMS) for the prevention of bacterial infections in patients who received bone marrow transplantation (BMT) for the treatment of solid and hematopoietic neoplasms. PATIENTS AND METHODS: Adult inpatients about to undergo BMT for lymphoma, leukemia, or solid tumors were enrolled onto a prospective, randomized, double-blinded, controlled trial that compared CIP (750 mg orally twice per day) with TMS (160 mg trimethoprim and 800 mg sulfamethoxazole orally twice per day). Subjects were stratified before randomization according to tumor and BMT type. Prophylaxis was begun within 96 hours of initiation of the BMT preparative regimen and continued until the onset of fever, signs or symptoms of infection, serious adverse effects, or recovery of the absolute granulocyte count (AGC) to > or = to 400/microL. RESULTS: Seventy-five CIP recipients and 71 TMS recipients were assessable for efficacy. No difference was noted between the two groups in occurrence of fever during neutropenia, time to onset of first fever, or overall infection rates. Ten bacteremias occurred in CIP recipients versus six in TMS recipients (P = .43). Ten episodes of Clostridium difficile enterocolitis occurred in TMS recipients versus no episodes in CIP recipients (P = .001). Four infections caused by gram-negative bacilli, including one bacteremia, occurred in TMS recipients versus none in CIP recipients (P = .06). No differences were noted in the incidence of rash or organ toxicity. TMS recipients had longer durations of granulocytopenia at AGC levels < or = to 500/microL and < or = to 100/microL than did CIP recipients (P = .08 for both comparisons). Mean peak and trough serum levels of CIP decreased significantly between weeks 1 and 2 of prophylaxis. CONCLUSION: CIP and TMS were equally safe and effective in the prevention of bacterial infections in BMT patients when the overall infection rate was used as the principal end point. TMS prophylaxis was associated with a higher incidence of C difficile enterocolitis and infections caused by gram-negative bacilli, as well as a trend toward prolongation of granulocytopenia.

Administration, Oral↗
PubMed1994

Use of the hypoxic cell sensitizer etanidazole (SR-2508) with intravenous melphalan and prednisone in the treatment of multiple myeloma: a pharmacokinetic study.

PURPOSE: A study was undertaken adding the alkylating agent sensitizer etanidazole to intravenous melphalan and oral prednisone for patients with multiple myeloma. This study explored the toxicity profile of these agents when given together and assessed the ability to attain adequate serum levels of etanidazole to permit sensitization to occur. METHODS AND MATERIALS: Etanidazole was administered intravenously in two doses of 3 g/m2 and 5 g/m2 90 min apart immediately prior to the administration of intravenous melphalan and oral prednisone for three consecutive cycles (total dose 24 g/m2). Patients received three additional cycles without etanidazole, allowing a comparison of hematologic toxicity from melphalan with and without etanidazole. RESULTS: Hematologic toxicity was moderate (Grade 3 or 4), but severity was similar during cycles with and without etanidazole. Only one patient developed a Grade 1 peripheral neuropathy questionably related to etanidazole. Most patients had etanidazole levels of > or = 70 ug/ml for 7 h, a level felt to be necessary for sensitization to occur. CONCLUSION: Etanidazole, administered as described, results in adequate serum levels for potential alkylating agent sensitization, without significant toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Phase I pharmacokinetic study of the hypoxic cell sensitizer etanidazole with carboplatin and cyclophosphamide in the treatment of advanced ovarian cancer.

PURPOSE: A Phase I study was undertaken to determine the maximum tolerated dose of the hypoxic cell sensitizer etanidazole which could be administered with carboplatin and cyclophosphamide, to determine whether adequate serum levels of etanidazole were achieved to allow for alkylating agent sensitization, and whether pretreatment with etanidazole altered carboplatin pharmacokinetics. METHODS AND MATERIALS: Patients received 2 g/m2 of intravenous etanidazole followed by a second dose of 4 g/m2 90 min later, followed by intravenous carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2) for four treatment cycles. Patients received an additional two cycles of carboplatin and cyclophosphamide without etanidazole. RESULTS: Two patients who received a total of 24 g/m2 of etanidazole developed Grade 1 neurotoxicity, and therefore etanidazole doses were not escalated further. The grade of granulocytopenia was worse after cycles with etanidazole than after those without (p = 0.03), but clinical outcome was not different. Etanidazole levels were adequate for alkylating agent sensitization (> 70 ug/ml) in all patients for the majority of the 7 h of testing. Pharmacokinetic data suggested t1/2 alpha and t1/2 beta for carboplatin were prolonged after pretreatment with etanidazole. CONCLUSION: Etanidazole, 2 g/m2 followed by 4 g/m2 90 min later, is safe and results in adequate serum levels for alkylating agent sensitization. Neurotoxicity appears to prevent dose escalation of etanidazole, and an interaction between etanidazole and carboplatin may have enhanced neurotoxicity in these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Timed-sequential high-dose cyclophosphamide and vincristine in the treatment of multiple myeloma.

BACKGROUND: This study was designed to examine the efficacy and toxicity of high-dose cyclophosphamide (CY), and to evaluate the potential added effect of vincristine (VCR) given at a theoretic time of malignant cell stimulation in a group of patients with multiple myeloma, refractory to or relapsing after, treatment with standard doses of chemotherapy. METHODS: Patients were randomly assigned to receive CY 2400 mg per M2 as a single-day dose and VCR 1.4 mg per M2 given on Day 1 or Day 9 after the CY. RESULTS: There were 108 cases suitable for analysis. No difference in objective response (17.6%, 23.5%), subjective response, remission duration, or survival was observed in the two treatment arms. CONCLUSIONS: The authors conclude that a single, high dose of cyclophosphamide is more toxic and provides equal or less response than the equivalent dose given over 4 consecutive days and that no improved effect was detected using timed-sequential therapy with VCR.

Aged↗
PubMed1994

Improved survival in patients with limited stage IIIA Hodgkin's disease treated with combined radiation therapy and chemotherapy.

PURPOSE: Patients with laparotomy-staged (PS) III 1A Hodgkin's disease confined to the upper abdomen are believed to have a favorable prognosis and require less aggressive treatment than patients with more-extensive stage III disease. We evaluated prognostic factors and outcome in 93 patients with PS III 1A Hodgkin's disease treated either with radiation therapy (RT) alone or combined RT and chemotherapy (combined modality treatment [CMT]) to determine the extent of treatment needed in this subgroup of stage IIIA patients. MATERIALS AND METHODS: We retrospectively reviewed the freedom from relapse (FFR) rate, sites of recurrence, and survival rate of PS III 1A patients selected to receive extended-field irradiation (MPA, n = 27), total-nodal irradiation (TNI, n = 34), and CMT (n = 32) between 1969 and 1987. CMT consisted of six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and MPA. Patients treated with MPA were part of a prospective trial designed to reduce treatment to patients with minimal stage III disease with very favorable characteristics. RESULTS: Histologic subclass and treatment were the only prognostic factors for FFR and survival rates. Patients with nodular sclerosis or lymphocyte predominance histology had significantly higher FFR and survival rates compared to patients with mixed-cellularity (MC) histology. The 10-year actuarial FFR of PSIII 1A patients treated with MPA was only 39%, versus 55% for TNI (P = .02) and 94% for CMT (v MPA, P < .0001; v TNI, P = .006). The patterns of recurrence in patients who received MPA and TNI were significantly different, with MPA patients relapsing more often in untreated pelvic or inguinal nodes, and TNI patients relapsing more often in extranodal sites with or without nodal sites. The 10-year actuarial overall survival rate for patients treated with CMT was 89% versus 78% for MPA (v CMT, P = .09) and 70% for TNI (v CMT, P = .05). CONCLUSION: Patients with PSIII 1A Hodgkin's disease treated with RT have a significantly higher risk of relapse and potentially a poorer survival compared with patients treated with CMT. These findings suggest that CMT should play a greater role in the treatment of this favorable substage of patients. Management with modified chemotherapy and RT in an attempt to reduce long-term treatment-induced complications may be a preferred approach for future trials.

Adolescent↗
PubMed1993

Concurrent radiation therapy and chemotherapy for locally unresectable squamous cell head and neck cancer: an Eastern Cooperative Oncology Group pilot study.

PURPOSE: The feasibility and success of an intensive chemoradiotherapeutic protocol for patients with locally advanced, unresectable squamous cell head and neck cancer was tested in this limited-institution, Eastern Cooperative Oncology Group phase II pilot study. MATERIALS AND METHODS: Between December 1987 and September 1989, 57 patients were entered onto this trial. The treatment protocol consisted of three courses of a 4-day continuous fluorouracil infusion, a single cisplatin bolus injection, and concurrent split-course radiotherapy. After 30 Gy of radiation and two chemotherapy courses, patients were evaluated for response and for the possibility of surgical resection. RESULTS: Fifty-five of 57 registered patients are assessable for toxicity and 52 are assessable for response and survival. Toxicity was significant, but tolerable, although there were three toxic deaths. A complete response to this treatment was ultimately achieved by 77% of patients. Twenty-four patients remain relapse-free. The projected Kaplan-Meier 4-year relapse-free survival rate is 45% and the overall survival rate is 49%. Median relapse-free and overall survival durations are 26 and 37 months, respectively. Of the 28 treatment failures, 79% were locoregional. Fourteen patients underwent surgery. Six remain relapse-free. CONCLUSION: This aggressive concurrent chemoradiotherapy protocol appears feasible within a cooperative group. Treatment results are promising and appear durable. A randomized phase III clinical trial is currently underway.

Adult↗
PubMed1992

Continuous-infusion cisplatin, 5-fluorouracil, and bolus methotrexate in the treatment of advanced non-small cell lung cancer.

BACKGROUND: Cisplatin and 5-fluorouracil have noted synergy in preclinical systems. The authors combined methotrexate with infusional cisplatin and 5-fluorouracil in an attempt to produce a regimen with improved activity in advanced NSCLC: METHODS: Twenty-six ambulatory patients with previously untreated non-small cell lung cancer were treated with continuous-infusion cisplatin (25 mg/m2/day for 5 days), 5-fluorouracil (800 mg/m2/day for 5 days), and intermediate-dose methotrexate (200 mg/m2 on days 15, 22), followed by leucovorin rescue (PFM regimen). RESULTS: Patients received a median of four cycles of therapy. Two patients had a complete response, and 10 had a partial response (overall response rate, 46.2% or 12 of 26). The median time to treatment failure was 22.5 weeks; the median survival was 55 weeks from the start of chemotherapy. There were no toxic deaths attributed to chemotherapy. Thrombocytopenia was the only Grade 4 toxicity (27%). Grade 1/4 and 2/4 peripheral neuropathy occurred in 17 of 26 patients (66%) and was associated with a cumulative cisplatin dose of more than 300 mg/m2. CONCLUSIONS: PFM (using continuous-infusion cisplatin) produced a high response rate but resulted in an high incidence of low-grade peripheral neuropathy.

Adult↗
PubMed1992

Long-term followup of 150 patients with testicular cancer treated at a single institution.

Between 1977 and 1988, 150 patients with disseminated primary testicular germ cell tumors were treated with cisplatin, vinblastine and bleomycin. Of the 150 patients 90 (60%) achieved a complete response to chemotherapy. An additional 33 patients achieved a complete response after removal of residual masses following chemotherapy. Thus, 123 of 150 patients (82%) achieved a disease-free status following chemotherapy with or without an operation. After a median followup of 49 months the estimated long-term probability of remaining without failure and of surviving is 77%. With this data base a multivariate analysis of prognostic factors determined the Indiana University staging system to be highly predictive. Other staging systems proved to be less useful. The subset of patients with minimal and moderate disease by Indiana staging containing mature teratoma in the orchiectomy specimen has a particularly excellent prognosis (99% actuarial survival) with chemotherapy.

Adolescent↗
PubMed1991

CT and pathologic predictive features of residual mass histologic findings after chemotherapy for nonseminomatous germ cell tumors: can residual malignancy or teratoma be excluded?

Forty-eight patients with disseminated nonseminomatous germ cell tumors were studied retrospectively to determine whether initial pathologic features and pre- and post-chemotherapy computed tomographic (CT) features could be used to exclude malignancy or teratoma in residual masses that were excised after chemotherapy. Neither CT findings (residual mass size, attenuation, and degree of shrinkage during chemotherapy) nor type of primary testicular tumor cell was significantly correlated with malignancy or teratoma versus necrosis in residual masses. No significant correlation was demonstrated between the combined features of (a) the absence of teratoma in a histologic specimen of the primary testicular tumor and (b) greater than 90% shrinkage of masses during chemotherapy and the absence of malignancy or teratoma in residual masses as suggested in the literature. Of nine patients with both of these findings, two had malignancy and two had teratoma. Radiographic and pathologic features cannot be used to reliably exclude malignancy or teratoma in residual abdominal masses after chemotherapy for nonseminomatous testicular cancer.

Adolescent↗
PubMed1990

Adaptive behavioral responses to potential infertility among survivors of testis cancer.

In a retrospective study of 153 testis cancer survivors, we examined the sociodemographic and clinical determinants of attitudes and behaviors toward illness-induced infertility. Five fertility adjustment responses were identified: sperm-banking awareness (SBA); adoption awareness (AA); fertility testing (FT); trying to father children (TFC); and fertility distress (FD). Although responses to infertility are multidetermined, these data demonstrate there is a distinct sociodemographic and clinical profile for the subgroups of men who engage in different fertility-related behaviors. Multivariate analysis results show that men most likely to be concerned with banking sperm are those who at diagnosis are younger (less than 35 years), childless, college educated, and whose relationships have become strained. Men who sought fertility tests were childless, college graduates, and able to ejaculate. The only factor predicting adoption was childlessness. Those married men attempting to father children were also less than 35 years of age at diagnosis and without ejaculatory dysfunction. The men at greatest risk for continued distress about infertility were those who remained childless and had posttreatment ejaculatory dysfunction. Residual infertility distress also was significantly associated with treatments that included extensive retroperitoneal lymph node dissection (RPLND) surgery, indicating that the latter is a "risk factor" in survivors' long-term distress. These data, while not definitive, show that the prerogative to have children is very important to men and that losing it sets into motion a range of both adverse emotions and adaptive responses. Adjustment to infertility is a complex process that begins at diagnosis and extends long after treatment is completed.

Adolescent↗
PubMed1990

Efficient design for estimation of median lethal dose and quantal dose-response curves.

The results of quantal dose-response experiments are often summarized by an estimate of the "median lethal dose," denoted LD50, and many sequential designs have been proposed for efficient estimation of LD50. These designs strive to produce a sequence of trials at dose levels that get closer and closer to LD50. Consequently, they may not provide very good estimates of the overall shape of the dose-response curve. In this paper we propose guidelines for the design of experiments that estimate LD50 fairly efficiently and that also allow for efficient global estimation of the curve.

Animals↗
PubMed1990

Reducing mean squared error in the analysis of pair-matched case-control studies.

The standard estimator of the common odds ratio for pair-matched case-control studies, the stratified estimate, is consistent but it ignores all information from the concordant pairs. At the other extreme, the pooled estimator is more efficient as it uses all the data, but is not consistent. In order to trade between bias and precision, Liang and Zeger (1988, Biometrics 44, 1145-1156) proposed an estimator that is a compromise between the stratified and pooled estimates. In the current paper, the possibility of optimizing the trade-off is explored. Specifically, the family of weighted averages of the stratified and pooled estimates is considered, and the weight that minimizes an asymptotic approximation of mean squared error is derived. In practice, the optimal weight must be estimated from the data so that the estimator is only approximately optimal. Small-sample properties are evaluated via simulations.

Bias↗
PubMed1989

Psychosocial factors, curative therapies, and behavioral outcomes. A comparison of testis cancer survivors and a control group of healthy men.

In a retrospective study of 223 testis cancer survivors and 120 controls matched sociodemographically, we examined the relative impact of sociodemographic and clinical factors on long-term outcomes in the areas of sexual function, relationships, employment, and mental outlook. For most of the survivors, testis cancer did not lead to unemployment (4.5%), divorce (6.8%), or disabling psychological problems. Multivariate analysis results confirm that cancer survivors report significantly more infertility and sexual performance distress, but not more desire distress, than the control group. Survivors' sexual impairment varied according to treatment received (and therefore histologic factors) and sociodemographic variables. Parental status (not having children) and education (college or less) independently predict infertility distress, whereas education and lower occupational level independently predicted sexual performance distress. Adjusting for socioeconomic status (SES), the men with advanced testis cancer who received chemotherapy and standard retroperitoneal lymph node dissection (RPLND) had significantly more infertility and performance distress than those men who received other treatments. Neither the treatment or SES variables predicted disrupted relationships or a deteriorated mental outlook. However, men with sexual impairment distress were more likely to report strained relationships and a pessimistic mental outlook. These findings have implications for treatment decisions and can be used to identify subgroups of survivors who could benefit from counseling and sexual rehabilitation services.

Adolescent↗
PubMed1988

Stage I nonseminomatous germ cell testicular tumor: prediction of metastatic potential by primary histopathology.

A study of 60 patients with clinical stage I nonseminomatous germ cell testicular tumor (NSGCT) was conducted to identify prognostic factors that may predict the likelihood of metastasis. Clinical features and histopathologic features of the primary testicular tumor were examined and analyzed for correlations with the presence of retroperitoneal nodal metastasis documented by surgery (N+) and with development of relapse (R+). Pathologic tumor stage greater than or equal to 2, with tumor extension into the tunica albuginea, rete testis, epididymis, or spermatic cord, was correlated with an increased rate of N+ compared with pathologic tumor stage I (P = .001). Vascular invasion was correlated with a higher rate of N+ (P = .05) and had a similar association with R+ (P = .08). Tumors containing less than 50% teratoma were found to have a higher rate of N+ than tumors with greater than or equal to 50% teratoma (P = .02). Based on the identified prognostic factors, a model for predicting the probability of retroperitoneal nodal metastasis in clinical stage I patients is proposed. The risk factors for nodal metastasis are: pathologic tumor stage greater than or equal to 2, vascular invasion, and less than 50% teratoma. Patients with none of the risk factors are considered at low risk and may be offered orchiectomy alone with surveillance for initial treatment. Patients with all three risk factors are at high risk and should be treated with a retroperitoneal lymph node dissection (RPLND) or possibly chemotherapy. Patients with one or two risk factors are at intermediate risk; it is recommended that they undergo RPLND. This risk model facilitates a rational approach to the management of clinical stage I NSGCT.

Adult↗
PubMed1988

Efficiency of balanced treatment allocation for survival analysis.

We assess the efficiency of balanced treatment allocation methods in clinical trials for comparing treatments with respect to survival. We compare optimal designs for each of three standard survival analysis techniques (maximum partial likelihood estimation, log-rank test, exponential regression) with balanced designs, over a range of hypothetical trials. Although balanced designs are not optimal, we find them to be very efficient. In view of the high efficiency demonstrated in this and in a previous paper (Begg and Kalish, 1984, Biometrics 40, 409-420), and practical difficulties in implementing an optimal design, we recommend the use of balanced allocation methods in practice.

Clinical Trials as Topic↗
PubMed1987

Management of patients with clinical stage I or II nonseminomatous germ cell tumors of the testis. Evolving therapeutic options.

Eighty patients with clinical stage I or II nonseminomatous germ cell tumors of the testis were managed with modified protocols, including modified nerve-sparing retroperitoneal lymph node dissection for patients with stage I cancer, retroperitoneal lymph node dissection for patients with low-volume stage II cancer, and initial chemotherapy with or without subsequent retroperitoneal lymphadenectomy for patients with high-volume stage II cancer. Patients with low-stage disease (clinical stage I) were treated successfully with modified retroperitoneal lymph node dissection (relapse rate, three of 40 patients). Clinical understaging was evidenced in 14 of 48 patients with clinical stage I disease who were found to have pathologic involvement of the retroperitoneal lymph nodes, including six patients with extensive retroperitoneal nodal involvement (pathologic stage B2). Of nine patients with retroperitoneal tumors less than 3 cm in diameter, four patients were satisfactorily treated with retroperitoneal lymph node dissection alone while five patients required chemotherapy after retroperitoneal lymph node dissection. Of 26 patients with retroperitoneal tumors 3 to 5 cm in diameter, 17 patients were treated with chemotherapy alone. All patients remain free of disease after the completion of definitive therapy. We conclude that therapeutic options should be modified based on histologic factors in the primary tumor, extent of retroperitoneal disease as indicated on a computed tomographic scan, and presence or absence of elevated tumor markers. By consideration these factors, optimum therapy can be selected to achieve the highest long-term survival rate with the least morbidity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

The impact of treatment allocation procedures on nominal significance levels and bias.

Complete randomization, the simplest method for allocating treatments to patients in clinical trials, can serve as a basis for inferential procedures using standard permutation tests, because the method ensures that each sequence of allocations is equally likely. No other method of allocation possesses this property. However, many clinical trials employ allocation methods that force balance of covariates across treatment groups. With these methods, some allocation sequences are impossible or highly unlikely so that standard permutation tests are technically invalidated. In this article we investigate whether standard permutation tests for binary outcomes are likely to yield distorted nominal p values in practical applications of these alternative allocation methods. A sample of completed trials conducted by the Eastern Cooperative Oncology Group serves as a basis on which to construct simulations. Our results indicate that nominal p values can be conservative, but are not likely to be severely distorted if the analysis is stratified by important covariates used as allocation prompts. Moreover the inherent conservativeness of exact methods due to discreteness tends to dominate any additional conservativeness due to nonrandom designs. In addition, we investigate the relationship of treatment allocation methods with bias in estimates from a logistic model when important covariates are unknown. This bias is the same for all asymptotically balanced allocation methods and is significant but not disastrous.

Analysis of Variance↗