Biomedical subjects

R Levitt

Publications and source records attributed to R Levitt.

At least 37 records · Page 2Linked to original sources

PubMed1997

Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia.

BACKGROUND: Randomized trials of colony-stimulating factors in febrile patients with neutropenia after chemotherapy have not consistently shown clinical benefit. Nevertheless, the use of colony-stimulating factors to treat patients with chemotherapy-induced neutropenia is widespread. METHODS: We performed a randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor (G-CSF) in afebrile outpatients with severe chemotherapy-induced neutropenia. We measured the number of days of neutropenia, rate of hospitalization, number of days in the hospital, number of days the patient received parenteral antibiotics, and number of culture-positive infections. RESULTS: We randomly assigned 138 patients to receive G-CSF (n=71) or placebo (n=67). The median time to an absolute neutrophil count of at least 500 per cubic millimeter was significantly shorter for patients who received G-CSF (two days, vs. four days for the patients given placebo). However, there was no effect on the rate of hospitalization, number of days in the hospital, duration of treatment with parenteral antibiotics, or number of culture-positive infections. CONCLUSIONS: Routine therapeutic application of G-CSF in afebrile patients with severe neutropenia can reduce the duration of neutropenia, but this does not appear to provide practical clinical benefit.

Adult↗

PubMed1997

Randomized trial of radiation therapy (RT) plus dibromodulcitol (DBD) versus RT plus BCNU in high grade astrocytoma.

PURPOSE: We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and DBD with RT and BCNU in patients with high-grade astrocytoma. METHODS: A total of 238 patients with supratentorial grade 3 and grade 4 astrocytoma were studied. Patients were stratified by age, extent of surgery, tumor grade, and performance score and randomly assigned to receive RT 55-60 Gy and either DBD, 200 mg/m2 orally on Days 1-10 every five weeks or BCNU, 200 mg/m2 intravenously every seven weeks. Median age was 60 years; 62% were 55 years or older. Eighty-three percent had subtotal resection, 58% had grade 4 tumors, and 83% had performance scores of 0-2. RESULTS: Survival distributions for all patients in the two arms were similar, with median survival of 41 weeks in each arm. Time to progression distributions were virtually identical, with medians of 22 weeks. BCNU produced significantly greater hematologic toxicity; median leukocyte and platelet nadirs on the first cycle were 3.6 vs. 4.7 (P = 0.0001) and 117 vs. 162 (P < 0.0001), and overall platelet nadirs were 80.5 vs. 114 (P = 0.0019). Non-hematologic toxicities were also significantly greater with BCNU, including nausea (57% vs. 31%; P < 0.0001) and vomiting (45% vs. 17%; P < 0.0001). CONCLUSION: This trial found no evidence of differences in treatment efficacy when either DBD or BCNU is combined with radiation therapy for patients with high-grade astrocytoma.

Algorithms↗

PubMed1997

Phase II trial of irinotecan in patients with metastatic colorectal carcinoma.

PURPOSE: To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT-11). PATIENTS AND METHODS: A total of 121 patients with advanced colorectal carcinoma--90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients--were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. RESULTS: Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy-naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11.9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with > or = grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (chi2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. CONCLUSION: According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.

Adenocarcinoma↗

PubMed1996

Phase II study of 5-fluorouracil and leucovorin in recurrent primary brain tumor.

Thirty patients with recurrent primary brain tumors were treated with a combination of 5-fluorouracil and leucovorin. There were three responses seen. Toxicity consisted of stomatitis, diarrhea, and hematological suppression. 5-fluorouracil and leucovorin would appear to be minimally effective in recurrent brain tumors.

Adult↗

PubMed1995

Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer.

PURPOSE: Gamma interferon has a wide range of properties, including the ability to sensitize solid tumor cells to the effects of ionizing radiation. The North Central Cancer Treatment Group has previously completed pilot studies of accelerated hyperfractionated thoracic radiation therapy (AHTRT) in patients with unresectable Stage IIIA/B nonsmall cell lung cancer (NSCLC). This Phase I study was designed to assess the toxicity of concomitant gamma interferon and AHTRT in a similar patient population. METHODS AND MATERIALS: Between December 1991 and May 1992, 18 patients with unresectable Stage IIIA/B NSCLC were treated with daily gamma interferon (0.2 mg subcutaneously) concomitant with AHTRT (60 Gy given in 1.5 Gy twice daily fractions). All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 with weight loss < 5%. Eight patients had Stage IIIA and 10 had Stage IIIB disease. RESULTS: Nine patients (50%) experienced severe, life-threatening, or fatal toxicities. Eight of the patients (44%) developed significant radiation pneumonitis, which was severe in six patients and fatal in two patients (11% treatment-related mortality). Two patients (11%) developed severe radiation esophagitis. With follow-up of 15-21 months, 2 patients are alive, and 16 have died. The median survival time and 1-year survival rate is 7.8 months and 38%, respectively. CONCLUSION: Gamma interferon appeared to sensitize normal lung tissue to the effects of radiation, as demonstrated by the high incidence of severe or fatal radiation pneumonitis. We do not recommend pursuing gamma interferon as a radiosensitizer in this setting.

Adult↗

PubMed1995

Myelodysplastic syndrome treatment with danazol and cis-retinoic acid.

We prospectively treated 46 patients with favorable myelodysplastic syndrome classified as refractory anemia (RA), refractory cytopenia (RC), or refractory anemia with ringed sideroblasts (RARS). These patients received one of two schedules of 13-Cis-Retinoic Acid (low dose 80 mg daily for 6 months vs. high dose 200 mg po daily for 3 months), or Danazol (800 mg po daily for 3 months), and were crossed over to the alternative drug in the absence of response or at progression. Using strict criteria of response we found little objective evidence of activity for either compound. Only two minor responses were seen among 22 patients treated with low dose 13-CRA, 1 response among 20 cases that received high dose 13-CRA, and 1 partial response and 1 minor response to Danazol among 34 cases. Neither 13-Cis-Retinoic Acid nor Danazol appear active enough in patients with favorable myelodysplastic syndrome to justify their use.

Aged↗

PubMed1995

Phase II study of amonafide in patients with recurrent glioma.

Amonafide, a novel imide derivative with broad preclinical antitumor activity, achieves significant cerebrospinal fluid levels in animal models. In order to test its antitumor activity in patients with recurrent diffuse infiltrative glioma of the astrocytic and oligodendroglial type, we performed a phase II clinical trial. Of the 22 eligible and evaluable patients treated, 2 (9%) experienced tumor regression lasting more than one year. No other patients experienced tumor regression; one remained stable more than six months. Toxicities consisted primarily of myelosuppression, vomiting, and venous irritation at the infusion site. We conclude that amonafide has minimal activity in recurrent glioma patients. Further investigations are not warranted in this study population.

Adenine↗

PubMed1995

Respiratory system mechanics in mice measured by end-inflation occlusion.

Characterization of pulmonary function parameters in mice will facilitate the dissection of genetic mechanisms underlying airway hyperresponsiveness. We evaluated acetylcholine (ACh)-induced respiratory system resistance (Rrs) and elastance (Ers) in A/J and C3H/HeJ mice and compared these results with the previously used airway pressure-time index (APTI). A low-dead-space ventilatory system was designed to ventilate anesthetized mice with constant inspiratory flow. The end-inflation occlusion method was used to measure Rrs and Ers at baseline and after intravenous ACh (12.5-75.0 micrograms/kg) challenge. ACh induced a dose-dependent rise in Rrs and Ers in A/J mice, whereas minimal changes were observed in C3H/HeJ mice. A/J mice had a higher baseline Rrs, yet the response to ACh was independent of baseline Rrs. Additionally, sequential ACh challenges led to augmented responses. Rrs, Ers, and APTI were strongly correlated, and each was useful to detect differences in interstrain cholinergic-induced airway responsiveness. The Rrs detected the smallest differences between the strains of mice studied.

Acetylcholine↗

PubMed1995

Opioid-induced muscle activity: implications for managing chronic pain.

OBJECTIVE: To increase awareness of opioid-induced involuntary muscle hyperactivity and to present management options. CASE SUMMARY: A ventilator-dependent 71-year-old man presented with pain caused by metastatic lung cancer. Transdermal fentanyl therapy was titrated to 200 micrograms/h. Two days later a continuous morphine infusion was initiated because of frequent administration of oral morphine solution for breakthrough pain. The patient became progressively less responsive and began exhibiting involuntary muscle hyperactivity thought to represent breakthrough pain. Despite the inability to assess pain control effectively in this unresponsive patient, the morphine infusion rate was increased from 22 to 717 mg/h within 7 days. No change in muscle hyperactivity was observed. DISCUSSION: Over the last decade involuntary muscle hyperactivity has been documented as an adverse effect of chronic opioid therapy. The literature describing the incidence of this toxicity, possible risk factors for its development, and recommendations for its management are discussed. CONCLUSIONS: The occurrence of muscle hyperactivity in an unresponsive patient receiving chronic opioid therapy may represent opioid toxicity. Recommendations for managing opioid-induced muscle hyperactivity include reduction of the opioid dosage and/or administration of clonazepam therapy.

Adenocarcinoma, Mucinous↗

PubMed1995

EMG feedback-assisted postoperative rehabilitation of minor arthroscopic knee surgeries.

This study assessed the effectiveness of surface integrated electromyographic (EMG) biofeedback in the rehabilitation of 51 patients undergoing minor arthroscopic knee surgery. Prior to surgery, both control (n = 23) and treatment (n = 28) groups received verbal and written explanations of postoperative isometric exercises; the treatment group received additional instruction in the use of ambulatory biofeedback equipment during exercise. Isokinetic tests of strength at approximately two weeks post-surgery revealed that patients given EMG biofeedback during postoperative exercise demonstrated significantly greater extensor torque and quadriceps muscle fiber recruitment than controls. Implications for the use of EMG biofeedback in long-term postoperative rehabilitation are discussed.

Adolescent↗

PubMed1994

Phase II evaluation of 5-fluorouracil and low-dose leucovorin in cisplatin-refractory advanced ovarian carcinoma.

Thirty-nine women with advanced, recurrent epithelial ovarian carcinoma who failed prior treatment with a platinum-based regimen were treated with leucovorin, 20 mg/m2 intravenously followed by 5-fluorouracil, 425 mg/m2 intravenously, daily for 5 consecutive days every 5 weeks in a phase II trial. Partial regressions were seen in 3 of 15 (20%) measurable disease patients, and objective regressions were seen in 3 of 14 (21%) evaluable/nonmeasurable disease patients. A 50% or greater decrease in CA-125 level was observed in 3 of 10 (30%) patients with no objectively evaluable or measurable disease. Overall objective response rate was 23% (95% confidence interval: 11 to 39%) in all 39 patients evaluated, with a median time to progression of 3 months and overall median survival of 7 months. Toxicities were acceptable and consisted of neutropenia, thrombocytopenia, stomatitis, and mild diarrhea. 5-Fluorouracil, as administered in this protocol, had modest antitumor activity in cisplatin-refractory ovarian carcinoma of short duration and minimal toxicity.

Adenocarcinoma↗

PubMed1994

Cyclophosphamide, cisplatin, and leuprolide acetate in patients with debulked stage III or IV ovarian carcinoma.

A phase II study of cyclophosphamide, cisplatin, and leuprolide acetate after debulking of stage III or IV ovarian carcinoma was conducted in 33 patients through a cooperative group study involving 11 institutions. The intent was to determine whether the addition of a gonadotropin-releasing hormone analogue would alter the response rates and toxicity profile of cyclophosphamide and cisplatin in patients with advanced ovarian cancer. Twenty-nine patients completed all 6 planned cycles. Of the 19 patients who had second-look laparotomy, 12 had persistent disease and 7 were negative for disease. The use of a gonadotropin-releasing hormone with combined chemotherapy did not alter the toxicity profile or the effectiveness of chemotherapy when comparisons were made with historical controls.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer.

PURPOSE: To compare two commonly used schedules of fluorouracil (5FU) and leucovorin in the treatment of patients with advanced metastatic colorectal cancer. Each of these dosage administration schedules has been demonstrated to be superior to single-agent bolus 5FU in previous controlled trials. PATIENTS AND METHODS: Three hundred seventy-two ambulatory patients with metastatic colorectal cancer were stratified according to performance status, and presence and location of any measurable indicator lesion(s). They were then randomized to receive chemotherapy with one of the following regimens: (1) intensive-course 5FU plus low-dose leucovorin (5FU 425 mg/m2 plus leucovorin 20 mg/m2 intravenous [IV] push daily for 5 days with courses repeated at 4- to 5-week intervals); (2) weekly 5FU plus high-dose leucovorin (5FU 600 mg/m2 IV push plus leucovorin 500 mg/m2 as a 2-hour infusion weekly for 6 weeks with courses repeated every 8 weeks). RESULTS: Three hundred sixty-two of 372 patients randomized (97.3%) were eligible and included in the analysis. Three hundred forty-six patients (95.6%) have died. There were no significant differences in therapeutic efficacy between the two 5FU/leucovorin regimens tested with respect to the following parameters: objective tumor response (35% v 31%), survival (median, 9.3 v 10.7 months), and palliative effects (as assessed by relief of symptoms, improved performance status, and weight gain). There were significant (P < .05) differences in toxicity, with more leukopenia and stomatitis seen with the intensive-course regimen, and more diarrhea and requirement for hospitalization to manage toxicity with the weekly regimen. Financial cost was also higher with the weekly regimen. CONCLUSION: Intensive-course 5FU plus low-dose leucovorin appears to have a superior therapeutic index compared with weekly 5FU plus high-dose leucovorin using the dosage administration schedules applied in this study based on similar therapeutic effectiveness, but lower financial cost, and less need for hospitalization to manage chemotherapy toxicity.

Aged↗

PubMed1994

Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer.

PURPOSE: We evaluated the effect of recombinant interferon gamma (rIFN-gamma) on survival and toxicity in small-cell lung cancer (SCLC) patients in complete remission (CR). PATIENTS AND METHODS: One hundred patients in CR following treatment with six cycles of combination chemotherapy, thoracic radiotherapy (TRT), and prophylactic cranial irradiation (PCI) were studied. All patients had been enrolled onto a cooperative group trial (North Central Cancer Treatment Group [NCCTG] 86-20-51). Patients received observation only or rIFN-gamma at a dose of 4 x 10(6) U subcutaneously per day for 6 months. RESULTS: Six patients (12%) did not comply with rIFN-gamma treatment. Substantial nonhematologic toxicities consisting of chills, myalgia, lethargy, and alteration of mood-personality were observed. No patient experienced life-threatening or fatal toxicity. The median times to progression for rIFN-gamma treatment or observation were 6.9 and 8.1 months (P = .54). The median survival times were 13.3 and 18.8 months, respectively (P = .43). Approximately 70% of all patients relapsed within 2 years. CONCLUSION: Time to progression and survival were inferior in patients treated with rIFN-gamma compared with randomized control subjects, although this difference was not statistically significant. These data indicate that rIFN-gamma treatment is not associated with a 33% improvement in survival (P = .04). Because of the high rate of relapse, SCLC patients in CR are an ideal group in which to evaluate novel and minimally toxic agents.

Adult↗

PubMed1991

A phase II evaluation of menogaril in cisplatin-refractory advanced ovarian carcinoma. A collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic.

Forty-one women with advanced, recurrent epithelial ovarian carcinoma (in whom prior chemotherapy with a platinum-based regimen failed) were treated with menogaril 200 mg/m2 intravenously every 4 weeks in a Phase II trial. Partial responses were seen in two of 19 (10.5%) measurable disease patients and three of 12 (25%) nonmeasurable but evaluable patients, an overall objective response rate of 16.1% (95% confidence interval, 5% to 34%). Median time to progression for all patients was 2 months and median survival, 5 months. Toxicities were acceptable and consisted primarily of leukopenia and gastrointestinal toxicity. Twenty-nine percent of the patients had venous irritation or painful phlebitis at the intravenous injection site. Menogaril, as administered in this protocol, had modest antineoplastic activity in previously treated ovarian carcinoma patients. The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment.

Adult↗

PubMed1991

Intellectual loss in Alzheimer's dementia and WAIS-R intrasubtest scatter.

Patterns of intrasubtest scatter in the WAIS-R protocols of patients (n = 32) with Alzheimer's disease were compared to those of normal elderly controls (n = 32). The Alzheimer's patients showed more randomly dispersed item failures on some subtests, but normal controls showed more intrasubtest variability on other measures. Rates of correct diagnostic classification based on scatter measures were only slightly better than chance despite the presence of prominent anomia, memory impairment, construction apraxia, and significant decline from premorbid intellectual level in demented patients. In contrast, demographically based estimates of intellectual loss produced accurate diagnostic classification in 81% of the cases. The incremental validity of qualitative scatter analysis in the evaluation of suspected Alzheimer's disease appears to be minimal.

Aged↗

PubMed1991

Phase II study of ifosfamide with mesna in adult patients with recurrent diffuse astrocytoma.

Sixteen patients who developed CT or MRI scan evidence of recurrent diffuse astrocytoma after radiation therapy and nitrosourea-containing chemotherapy received ifosfamide (2500 mg/m2/day for 3 consecutive days) and mesna (500 mg/m2/dose, 5 doses/day for 3 consecutive days). Toxicity consisted primarily of leukopenia in that 60 percent of patients developed leukocyte nadirs less than 1500/mcL. Excessive somnolence occurred in three patients and may have contributed to a case of fatal pneumonia in one patient but was reversible in the other two. No patient had CT or MRI scan evidence of tumor regression. One patient remains stable at 11.3 + months, but all other patients developed evidence of progressive disease less than 6 months from initiation of therapy. The median times to tumor progression and death were 2.0 and 4.8 months, respectively. In conclusion, while ifosfamide and mesna can be given safely at this dose and schedule, there is no evidence of antitumor effect. The degree of leukopenia observed likely would prevent further dose escalation of ifosfamide or addition of other myelosuppressive agents without additional means of bone marrow support in this population of patients.

Adolescent↗

PubMed1991

Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer.

In a previous study (J Clin Oncol 7:1407-1417, 1989), we identified two dosage administration schedules of fluorouracil (5FU) combined with leucovorin that were superior to single-agent 5FU for the treatment of advanced colorectal cancer. In this same study, a regimen of 5FU plus high-dose methotrexate (MTX) demonstrated a suggestive advantage over 5FU alone. To permit a more definitive comparison, we have extended our evaluation of these three regimens to involve an additional 259 patients. In all, 457 patients with advanced colorectal cancer were randomly assigned to one of the following regimens: 5FU plus low-dose leucovorin, 5FU plus high-dose leucovorin, or 5FU plus high-dose MTX with leucovorin rescue. We have found that each of the 5FU/leucovorin regimens demonstrates a significant (P less than or equal to .01) advantage over 5FU plus high-dose MTX for objective tumor response and interval to tumor progression. Moreover, 5FU plus low-dose leucovorin confers a significant survival benefit (P less than or equal to .01) compared with 5FU plus high-dose MTX. The 5FU plus high-dose leucovorin regimen shows a survival benefit only in unadjusted analyses (P = .04), but this difference is not significant when adjusted for imbalances in prognostic variables (P = .44). Evaluation of the two 5FU/leucovorin regimens rules out a 10% decrease in death rate for the high-dose leucovorin regimen compared with the low-dose leucovorin regimen (P less than .05). The regimen of 5FU plus low-dose leucovorin has now been shown to offer a statistically significant survival advantage versus 5FU alone and versus 5FU plus high-dose MTX, a regimen that had shown promise in earlier trials. These data confirm the efficacy of leucovorin combined with 5FU in patients with advanced colorectal cancer and establish that it is not necessary to use high doses of leucovorin to achieve these results.

Aged↗