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Biomedical subjects

R Feld

Publications and source records attributed to R Feld.

At least 37 records · Page 2Linked to original sources

Once-daily therapy with ceftriaxone compared with daily multiple-dose therapy with cefotaxime for serious bacterial infections: a randomized, double-blind study.

A randomized, double-blind study was done to compare the efficacy and toxicity of daily single-dose therapy with intravenous ceftriaxone (2 g every 24 h) with daily multiple-dose therapy with cefotaxime (2 g every 6 h) for treatment of serious bacterial infections in nonneutropenic patients. Of the 325 patients who were evaluable for toxicity, 241 (74.2%) were evaluable for efficacy. Infection sites included lung (106), urinary tract (42), skin and soft tissue (43), bone and joint (23), bacteremia (21), and hepatobiliary (5). Definite infections were present in 173 cases (71.8%) and possible infections in 68 (28.2%). Analysis of clinical and bacteriologic responses and adverse drug reactions showed no significant differences between the regimens. Values for 95% confidence limits on the differences between regimens for positive clinical and bacteriological outcomes in definite infections were -0.8% to 3.0% and -1.9% to 9.1%, respectively. Thus, daily single-dose therapy with ceftriaxone was comparable to daily multiple-dose therapy with cefotaxime in treating these bacterial infections.

Adult

Carcinoembryonic antigen, arginine vasopressin and calcitonin as markers of early small-cell lung cancer relapse.

Patients with small-cell lung cancer (SCLC) underwent serial blood monitoring during remission: 66 were tested for carcinoembryonic antigen (CEA) and calcitonin (CTN), including 40 who were concomitantly tested for arginine vasopression (AVP) as well. 83% of the patients had at least one assay elevated prior to induction therapy. By serial monitoring, blood concentrations reflected disease course and reached lowest levels at remission. CEA, AVP and CTN shifted along the course of disease independently of each other; a normal pretreatment titer did not preclude its rise at a later phase, while an initially elevated assay could normalize at remission and stay normal thereafter. The median lead time (LT) to clinically diagnosed relapse, for limited-disease patients, was 229 days for complete and 90 days for partial remitters. Patients with extensive disease had similar LT values. LT to local recurrence was shorter than to distant relapse. Remission AVP titers of up to 6 ng/ml conferred disease-free survival (DFS) longer than that associated with higher titers (median DFS 518 vs. 211 days, respectively; p = 0.045 for curve differences). The relative risk (RR) of relapse associated with pretreatment patient characteristics and with absence or presence of tumor marker normalization at remission was estimated by the Cox proportional hazards model. This analysis revealed that the RR of relapse conferred by pretreatment attributes, e.g. disease extent, was considerably modified by biochemical co-variates at remission, e.g. serum CEA level relative to a 3 ng/ml cutoff point.

Arginine Vasopressin

Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients.

Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma (DMM) seen at large centers in Ontario and Quebec from 1965 to 1984 were reviewed retrospectively. Previous asbestos exposure was found in 44% of patients. Diagnosis was most often made by exploratory thoracotomy; pleural biopsy or cytology were rarely contributory. The delay in diagnosis was often long (median time, 3.5 months) and thrombocytosis (platelets greater than or equal to 400,000/microL) was common (41% of cases). The median survival (MS) was only 9 months. Eleven clinical variables were analyzed for prognostic significance. The three most important prognostic factors using a univariate analysis were stage, weight loss, and histologic type. For 118 patients with complete data, multivariate analysis showed that the stage of disease, high platelet count, and asbestos exposure were the most important prognostic factors. There was no cure of DMM, and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures. Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents. This large retrospective trial can serve as a baseline for future studies in this field. In particular, it provides the basis for appropriate stratification variables to be used in future therapeutic trials.

Adult

A prospective study of adjuvant surgical resection after chemotherapy for limited small cell lung cancer. A University of Toronto Lung Oncology Group study.

Seventy-two patients with limited small cell lung cancer were identified as candidates for adjuvant operation after chemotherapy. All patients received preoperative chemotherapy with cyclophosphamide, doxorubicin HCl (Adriamycin), and vincristine, or the epipodophyllotoxin derivative VP-16 and cisplatin. The rate of response to chemotherapy was 80% (complete response 38% and partial response 42%). After chemotherapy, 57 patients (79.1%) were candidates for adjuvant surgical resection, but only 38 underwent thoracotomy. Eight required a pneumonectomy, 25 a lobectomy, and five patients had no resection. Postoperative pathologic study revealed only small cell lung cancer for 29 patients, mixed and non-small cell lung cancer for two, non-small cell lung cancer for four, and no residual tumor in three patients. Pathologic staging revealed seven patients in stage I (N0), nine in stage II (N1), and 22 in stage III. The median survival time for the 38 surgical patients was 91 weeks and projected 5-year survival rate 36%. Patients with pathologic stage I disease had significantly longer survival times (median not reached) than did patients in stage II or stage III (median survival 69 and 52 weeks, respectively). Within the group not undergoing operation, 19 patients responded to therapy and were eligible for adjuvant surgical resection, but did not undergo thoracotomy (10 patients were randomized to radiation only, and nine patients refused operation). Their median survival of 51 weeks was inferior to that of the 38 surgical patients (p = 0.049). Adjuvant surgical resection after chemotherapy resulted in long-term survival and cure for a significant proportion of patients with pathologic stage I disease. A significant improvement in survival could not be documented for patients in stages II and III. Intensive pretreatment investigation including mediastinoscopy is essential to exclude patients who will not benefit from adjuvant surgical resection.

Adult

The compromised host.

A short review on infections in all types of immunocompromised host is given. This includes aspects dealing with the underlying diseases that predispose to infection, other predisposing factors to infections, and the types of infections that different compromised hosts are susceptible to and why. An attempt is made to lead into a more detailed discussion about the specific compromised hosts that are discussed in the rest of the symposium.

Humans

Risk factors for varicella zoster disseminated infection among adult cancer patients with localized zoster.

Varicella zoster (VZ) infection can be a highly morbid and potentially fatal disease among immunocompromised patients; 811 episodes of VZ infection among adult cancer patients seen at the Princess Margaret Hospital from 1970 to 1980, were identified. Seven hundred twelve patients with first episodes of localized VZ infection (zoster) were analyzed for potential risk factors for dissemination. Significant risk factors after univariate analysis included the diagnosis of Hodgkin's disease, decreasing age, chemotherapy within 6 months of VZ infection, and extensive tumor at initial tumor diagnosis. Complete tumor remission at the time of infection, previous radiotherapy, and breast or gynecologic cancer were associated with reduced risk in this analysis. After multivariate analysis the following factors were independently associated with increased risk: Hodgkin's disease (P less than 0.001), non-Hodgkin's lymphoma (P = 0.016), and head and neck cancer (P = 0.043). Complete tumor remission and previous radiotherapy were again related to a reduced risk of infection. This study identifies risk factors that define specific subgroups of adult cancer patients with zoster infections who are at increased risk for VZ dissemination. These factors may be useful in prospectively defining high-risk groups in the design of antiviral therapy trials and may have a role in deciding which cancer patients with zoster will benefit most from receiving antiviral therapy to prevent dissemination.

Adolescent

Intracranial recurrence of carcinoma after complete surgical resection of stage I, II, and III non-small-cell lung cancer.

We retrospectively analyzed the risk of intracranial recurrence of cancer in 1532 patients who were surgically treated between 1977 and 1986 for Stage I, II, or III non-small-cell lung cancer, after rigorous surgical and pathological staging. This analysis was undertaken as a background for a possible randomized clinical trial of prophylactic cranial irradiation in such patients. One hundred four patients (6.8 percent) had documented first recurrences involving the brain, including 98 patients (6.4 percent) in whom the brain was the sole site of first recurrence. Sixty patients (3.9 percent) had only intracranial involvement at the time of death. Prognostic variables that had a significant effect on the time to recurrence in the brain were histologic features of the carcinoma (patients with nonsquamous-cell cancers were more at risk than those with squamous-cell cancer), the T1N1/T2N0 and T2N1 staging subsets (T1, tumor less than or equal to 3 cm in diameter; T2, tumor greater than 3 cm; N0, no regional lymph-node metastasis; N1, ipsilateral hilar-lymph-node metastasis), and initial weight loss of more than 10 percent. We conclude that prophylactic cranial irradiation would at best benefit only a very small subset of these patients. We believe, therefore, that neither prophylactic cranial irradiation nor a randomized trial is indicated in patients with non-small-cell lung cancer who have undergone complete resection.

Brain Neoplasms

The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a Canadian Multicenter Randomized Trial.

Patients with limited stage small cell lung cancer were initially randomized to receive either three courses of Cyclophosphamide, Adriamycin, and Vincristine (CAV) followed by three courses of VP-16 and Cis-platin (VP-PT) or six courses of alternating CAV and VP-PT. Responding patients received prophylactic cranial radiation (PCI) after three courses of chemotherapy (CT) and loco-regional thoracic radiation (LRTR) after six courses. No maintenance chemotherapy was given. Patients receiving LRTR were randomized to receive either 25 Gy in ten fractions over 2 weeks (SD) or 37.5 Gy in 15 fractions over 3 weeks (HD). In both arms the pre-chemotherapy disease was treated with a 2 cm margin around the primary tumor volume. The mediastinum was included in the treatment volume and the supraclavicular nodes were also included if involved originally. The spinal cord was shielded after 32 Gy. Of the 333 patients enrolled by the time the trial closed in October 1984, 168 were eventually randomized to LRTR and are eligible for response assessment. The overall response rate after combined RT and CT was 94% (CR 67%, PR 27%). The CR rate for SD was 65% and for HD 69%. The combined treatment was well tolerated by most patients. Forty-nine percent of HD patients developed dysphagia compared to 26% of those SD (p less than 0.01). At the time of this analysis the median duration of follow-up since randomization to radiotherapy is 30 months. The median local progression-free survival on HD is 49 weeks. On SD it is 38 weeks (p = 0.05, one sided). The actuarial incidence of local progression by 2 years is 69% on HD and 80% on LD. There is as yet no significant difference in overall survival between the two arms. It appears that HD radiotherapy as administered in this study may have an impact on local control, but it is too early to determine if this will translate into a survival benefit.

Adult

VP-16 and carboplatin in previously untreated patients with extensive small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group.

Thirty-four previously untreated patients with extensive small cell lung cancer were treated with a combination of carboplatin 300 mg m-2 i.v. on day 1 and etoposide 100 mg m-2 i.v. on days 1, 2 and 3 every 28 days. Thirty-two patients were assessable for response. Eighteen patients (56%) achieved an objective response (95% confidence limits 38%-73%). Five (16%) had a complete response and 13 (41.0%) had a partial response. The median time to response was 7.8 weeks and the median duration of response was 23.1 weeks (range 6.2 to 54 weeks). The median survival of all 34 extensive disease patients was 34.7 weeks (range 1.3-59.3 weeks). Myelosuppression (leukopenia) was the main toxicity. There was one early death that may have been treatment-related. Biochemical renal dysfunction was noted in two patients. Paresthesiae and tinnitus/hearing loss were described by three and two patients respectively. Serious gastrointestinal toxicity was infrequent. This and other studies have shown this combination to be active and well tolerated in small cell lung cancer; however, it is not yet clear if it is as efficacious as the more commonly used VP-16-cisplatin regimen.

Adult

Cefoperazone compared with ampicillin plus tobramycin for severe biliary tract infections.

In a prospective, randomized, multicenter study, the efficacy and safety of cefoperazone and the combination ampicillin-tobramycin as initial therapy for patients with severe acute biliary tract infections were compared. Of 77 patients initially entered in the study, definite severe biliary tract infection was confirmed in 67. Sixty-four patients completed treatment. At the end of treatment, 35 of 36 (97%) patients given cefoperazone and 23 of 28 (82%) given ampicillin-tobramycin were cured of their infection (P = 0.07). Pathogens were recovered from the bile in 32 patients; microbiological cures were observed in 18 of 19 (94%) patients receiving cefoperazone and 8 of 13 (62%) receiving ampicillin-tobramycin (P = 0.03). Thirteen patients had septicemia. None (0%) of the eight septicemic patients from the cefoperazone group, but two of five (40%) from the ampicillin-tobramycin group, were clinical failures. Of the isolated pathogens, 51% were resistant to ampicillin, while the resistance rate was 4% for tobramycin and 1% for cefoperazone (P less than 0.001). Biliary concentrations of cefoperazone were maintained at high levels--236 +/- 87 micrograms/ml up to 12 h after administration. Even in the presence of severe obstruction, cefoperazone levels in the bile and gallbladder wall were above MICs for most pathogens. Cefoperazone may be considered as an excellent alternative in the therapy of severe biliary tract infections.

Acute Disease

Cost-effectiveness of cancer chemotherapy: an economic evaluation of a randomized trial in small-cell lung cancer.

An economic evaluation of a randomized trial of cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and vincristine alone or alternating with etoposide (VP-16) and cisplatin in extensive small-cell lung cancer (SCLC) was undertaken. A survival benefit of 1.6 months in favor of alternating chemotherapy was associated with an additional cost of $450 (1984 Canadian dollars) per patient. This translated to a cost of $3,370 per year of life gained. Sensitivity analyses demonstrated that the cost-effectiveness (CEA) of alternating chemotherapy was greatest when treatment was given on an outpatient basis. The results of the evaluation were sensitive to hospitalization rates, but even the most unfavorable analyses revealed the CEA of alternating chemotherapy to be comparable to that of treatments of common nonmalignant diseases. It is concluded that the CEA of alternating chemotherapy for SCLC was favorable when compared with accepted treatments for nonmalignant diseases. The survival benefit seen with alternating chemotherapy was felt to be clinically significant and alternating chemotherapy is recommended as routine therapy for extensive SCLC.

Antineoplastic Combined Chemotherapy Protocols