bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel chemotherapeutic agents in the treatment of non-small-cell lung cancer.
Authors: Lilenbaum R C , Green M R 
Published: February 2017

PURPOSE This study attempted to identify novel chemotherapeutic agents with greater than 15% activity in non-small-cell lung cancer (NSCLC). DESIGN An English language literature search, which included abstracts and original articles, and a review of bibliographies of identified articles, were used. RESULTS Nine new agents, analogs, or old agents used in new doses or schedules were identified: CPT-11, topotecan, taxol, taxotere, Navelbine (Burroughs Wellcome, Research Triangle Park, NC), chronic oral etoposide, edatrexate, gemcitabine, and high-dose epirubicin. Results of phase I and II trials that involved these agents alone or as part of combination regimens are presented. CONCLUSION Several new chemotherapeutic agents with activity against NSCLC are now available. Response rates compare favorably with those of available standard drugs. These new drugs are being integrated into multiagent combinations. Large-scale phase III trials that compare these new combinations with current standard approaches will be necessary to determine whether or not these new drugs will have a positive impact on survival in patients with NSCLC.
Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B.
Authors: Chahinian A P , Antman K , Goutsou M , Corson J M , Suzuki Y , Modeas C , Herndon J E , Aisner J , Ellison R R , Leone L 
Published: February 2017

PURPOSE The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II multicenter trial to evaluate the activity of two cisplatin-containing regimens (cisplatin and mitomycin [CM], or cisplatin and doxorubicin [CD]) in patients with malignant pleural or peritoneal mesothelioma (protocol CALGB 8435). PATIENTS AND METHODS Seventy-nine patients were entered between June 1984 and October 1986. Eligibility included a performance status of 0 to 2 by CALGB criteria, and no prior chemotherapy. Central pathology review was performed. Randomization was stratified according to the cell type (epithelial v mixed or sarcomatous) and the presence of measurable versus assessable disease. Of the 79 patients entered, 70 were included in this analysis (35 on CM and 35 on CD), including 48 with epithelial cell type and 22 with mixed or sarcomatous cell types. Sixty-six patients had pleural mesothelioma and four had peritoneal mesothelioma. There were 34 cases with measurable disease and 36 with assessable disease. RESULTS The overall response rate was 26% for CM (two complete responses [CRs], three partial responses [PRs], and four regressions) and 14% for CD (four PRs and one regression). Median time to treatment failure was 3.6 months for CM and 4.8 months for CD, and median survival duration from study entry was 7.7 and 8.8 months, respectively, with no significant differences between treatments. Good performance status (0 or 1) was associated with significantly longer survival duration (P = .013). Both regimens were well tolerated and there were no treatment-related deaths due to toxicity. CONCLUSION Moderate antitumor activity has been observed with both regimens. In this randomized phase II trial, the overall response rates, time to treatment failure, and overall survival appear to be similar for the two regimens tested.
Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy.
Authors: Tepler I , Cannistra S A , Frei E , Gonin R , Anderson K C , Demetri G , Niloff J , Goodman H , Muntz H , Muto M 
Published: February 2017

PURPOSE Attempts to increase dose-intensity in clinical practice have been limited by cumulative hematologic toxicity despite the use of hematopoietic growth factors. To address this problem, we designed a study to determine whether four cycles of dose-intensive chemotherapy with carboplatin could be administered in the outpatient setting using granulocyte-macrophage colony-stimulating factor (GM-CSF) and peripheral-blood progenitor cells (PBPCs) that had been harvested before initiation of treatment. PATIENTS AND METHODS An initial cycle (cycle no. 0) of cyclophosphamide 4 g/m2 followed by GM-CSF was used to mobilize PBPCs harvested by leukapheresis for 6 consecutive days. Cycles no. 1 through 4 consisted of outpatient carboplatin 600 mg/m2 and cyclophosphamide 600 mg/m2 followed by GM-CSF 5 micrograms/kg subcutaneously (SC) twice per day every 28 days. In cycle no. 1, PBPC were not reinfused to assess the effects of GM-CSF alone. In cycles no. 2 through 4, PBPCs were reinfused on day 3 in an outpatient setting. RESULTS In eight assessable patients, the addition of PBPCs in cycle no. 2 resulted in a significant reduction in the median duration of thrombocytopenia less than 20,000/microL (6.5 v 1 day; P = .016), days to platelets more than 50,000/microL (20.5 v 15 days; P = .020), number of platelet transfusions (five v 1.5; P = .016), and duration of neutropenia (absolute neutrophil count [ANC] < 1,000/microL (7 v 2.5 days; P = .008) when compared with cycle no. 1. Dose-limiting hematologic toxicity, defined as more than 7 days of platelets less than 20,000/microL or ANC less than 500/microL, was observed in four of eight patients during cycle no. 1, but not during cycles no. 2, 3, and 4 of chemotherapy supported by PBPCs (a total of 19 cycles in eight patients). Five of eight patients completed all four cycles of high-dose therapy. Three patients did not complete four cycles due to late thrombocytopenia (n = 2) or tumor progression (n = 1). CONCLUSION These results indicate a benefit of PBPCs in addition to GM-CSF in alleviating myelosuppression of dose-intensive chemotherapy. Initial collection of PBPCs may allow administration of repetitive cycles of high-dose chemotherapy with acceptable toxicity to outpatients at disease onset.
Extended administration of oral etoposide and oral cyclophosphamide for the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study.
Authors: Grunberg S M , Crowley J , Livingston R , Gill I , Williamson S K , O'Rourke T , Braun T , Marshall M E , Weick J K , Balcerzak S P 
Published: February 2017

PURPOSE We designed an all-oral regimen of etoposide and cyclophosphamide for use in advanced non-small-cell lung cancer. PATIENTS AND METHODS Eligible patients were chemotherapy-naive and had histologically confirmed assessable or measurable stage IV non-small-cell lung cancer. Patients received etoposide 50 mg/m2/d orally days 1 through 14 and cyclophosphamide 50 mg/m2/d orally days 1 through 14 every 28 days. Doses on later cycles were adjusted for myelosuppression. RESULTS Sixty-six patients (64 eligible patients) received 192 cycles of oral extended etoposide/cyclophosphamide therapy (median, two cycles; range, zero to 15). Therapy was well tolerated with the mean dose per cycle being 104% of the originally scheduled dose. Two patients (3%) achieved a complete response and six (9%) achieved a partial response. Leukopenia, anemia, nausea/vomiting, and alopecia were the most common toxicities. Median survival was 6 months, and the 1-year survival rate was 25.6%, comparable to more intensive treatments. CONCLUSION Oral extended etoposide/cyclophosphamide is a well-tolerated alternative for the treatment of stage IV non-small-cell lung cancer and can be used as a basis for the design of further outpatient regimens.
Novel oral combination chemotherapy in the treatment of intermediate-grade and high-grade AIDS-related non-Hodgkin's lymphoma.
Authors: Remick S C , McSharry J J , Wolf B C , Blanchard C G , Eastman A Y , Wagner H , Portuese E , Wighton T , Powell D , Pearce T 
Published: February 2017

PURPOSE To determine the toxicity, response, and survival rate of orally administered combination chemotherapy in patients with AIDS-related intermediate- and high-grade non-Hodgkin's lymphoma. Secondary objectives included prospective quality-of-life assessment and quantitation of cell-associated p24 antigen (p24 Ag) by flow cytometry. PATIENTS AND METHODS Eighteen patients with biopsy-proven lymphoma were treated with oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, etoposide 200 mg/m2 on days 1 through 3; cyclophosphamide 100 mg/m2 on days 22 through 31, and procarbazine 100 mg/m2 on days 22 through 31 at 6-week intervals. A variety of clinical assessments were performed: prospective quality-of-life assessment using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments; indirect immunofluorescence with flow cytometry to measure cell-associated p24 antigen; and price of the oral regimen compared with two other intravenous combination chemotherapy regimens. RESULTS The overall objective response rate using Eastern Cooperative Oncology Group (ECOG) criteria was 61% (95% confidence interval, 39% to 84%), with seven complete remissions (39%) and four partial remissions (22%). The median survival duration was 7 months, with a range of 11 days to 36 months. The treatment-related mortality rate was 11%. One patient developed CNS progression. Myelosuppression was the most frequent and severe toxicity encountered. Predictor variables of performance status (PS), prior history of thrush, and CD4 lymphocyte count were found to be of prognostic value. In a separate analysis, scores on the three subscales of the BSI were also found to be predictive of complete response. The price of this regimen is several thousand dollars less than that of other intravenous combination chemotherapy regimens. CONCLUSION This regimen is active in patients with AIDS-related non-Hodgkin's lymphoma. Because it is important to design systemic cytotoxic chemotherapy regimens that are cost-effective, considerate of quality-of-life issues, and efficacious in this patient population, this approach should be compared with standard intravenous combination chemotherapy regimens in randomized controlled clinical trials.
Secondary neoplasms following treatment of malignant germ cell tumors.
Authors: Bokemeyer C , Schmoll H J 
Published: February 2017

PURPOSE The current study investigates the frequency and outcome of secondary malignancies in patients treated for testicular cancer at Hannover University Medical School between 1970 and 1990. PATIENTS AND METHODS One thousand twenty-five patients with a median follow-up duration of 61 months (range, 12 to 240) were included in the analysis. Follow-up was complete in 1,018 patients (99%). Histology was seminoma in 324 patients (38.7%) and nonseminomatous germ cell tumor in 624 patients (61.3%). At the time of median follow-up, 814 patients (79.9%) were alive. RESULTS Fourteen patients developed a secondary neoplasm (cumulative incidence, 1.38%; 95% confidence interval [CI], 0.75 to 2.30); 13 patients had solid tumors and one had secondary lymphoblastic leukemia with a t(4; 11) translocation including band 11q23. None of 224 patients on surveillance strategy (with or without retroperitoneal lymph node dissection [RPLND]) developed a second neoplasm, compared with four of 413 patients (0.97%; 95% CI, 0 to 1.9) after cisplatin-based chemotherapy (not significant) and nine of 332 patients (2.7%; 95% CI, 0.9 to 4.5) after radiotherapy (P = .02). The cumulative incidence of a secondary neoplasia of 1.76% (95% CI, 0.97 to 2.94) in patients treated by radiotherapy and/or chemotherapy was significantly higher compared with patients on surveillance protocols (P = .03). Chemotherapy containing standard-dose etoposide did not increase the risk of occurrence of secondary neoplasms. A significantly elevated relative risk of 7.53 (range, 3.4 to 14.3) compared with the male German population was only found for patients treated by radiotherapy. CONCLUSION Compared with patients who have other curable malignant tumors, an incidence of 1.38 of secondary neoplasms after a median follow-up duration of 61 months is low. The highest risk for secondary neoplasia after treatment of testicular cancer is associated with the use of radiotherapy. Following chemotherapy, no significantly elevated risk was observed. In conclusion, the benefits of curative treatment far outweigh the risk of secondary cancer in patients with malignant germ cell tumors.
Clinical trial of Serratia marcescens extract and radiation therapy in patients with malignant astrocytoma.
Authors: Black K L , Ciacci J D , Ammirati M , Selch M T , Becker D P 
Published: February 2017

PURPOSE A clinical trial was undertaken to determine the safety and efficacy of combining a biologic response modifier derived from the bacterium Serratia marcescens (ImuVert) and radiation therapy (RT) in patients with newly diagnosed anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM). PATIENTS AND METHODS Fifteen patients who had undergone either a gross total resection, a partial resection, or a biopsy were treated concurrently with ImuVert and RT. Safety and tolerance were examined by assessment of symptomatic reactions recorded at each ImuVert treatment. Efficacy of treatment was examined in terms of time to progression of tumor and survival. RESULTS All patients experienced local reactions at the injection sites that consisted of erythema and induration. The majority of patients experienced flu-like symptoms. Hypotension was responsible for the most significant morbidity (which required fluid resuscitation and extended observation) and dose deescalation. No patients were removed from the study because of toxicity. There were no on-study deaths related to ImuVert treatment. Median time to progression was 33.4 weeks, and median survival was 78 weeks. CONCLUSION These results compare favorably with those of recent studies in patients with malignant astrocytomas who received multimodality therapy.
Phase I study of high-dose piroxantrone with granulocyte colony-stimulating factor.
Authors: Savarese D M , Denicoff A M , Berg S L , Hillig M , Baker S P , O'Shaughnessy J A , Chow C , Otterson G A , Balis F M , Poplack D G 
Published: February 2017

PURPOSE We performed a phase I trial of piroxantrone with and without granulocyte colony-stimulating factor (G-CSF) to determine whether the use of this cytokine would enable us to increase the dose-intensity of piroxantrone. PATIENTS AND METHODS Thirty-eight patients received 121 courses of piroxantrone administered once every 21 days. Initial patient cohorts received piroxantrone alone starting at 150 mg/m2 and the dose was escalated in subsequent patients until dose-limiting toxicity (DLT) was reached. Patient cohorts then received escalating doses of piroxantrone starting at 185 mg/m2 administered with G-CSF beginning day 2. RESULTS Dose-limiting neutropenia occurred in three of six patients treated with 185 mg/m2 piroxantrone; the maximum-tolerated dose (MTD) of piroxantrone alone was 150 mg/m2. Three of six patients treated with piroxantrone and G-CSF exhibited dose-limiting thrombocytopenia at 445 mg/m2; the MTD of piroxantrone with G-CSF was thus 355 mg/m2. Seven patients developed symptomatic congestive heart failure (CHF) at cumulative piroxantrone doses ranging from 855 to 2,475 mg/m2 and two have died of cardiotoxicity. Of these patients, six of seven had previously received doxorubicin. Other nonhematologic toxicity was mild. CONCLUSION The use of G-CSF results in a more than twofold increase in the MTD of piroxantrone. However, symptomatic cardiotoxicity is prominent, especially in patients who have received prior treatment with anthracyclines.
Home antibiotic therapy for low-risk cancer patients with fever and neutropenia: a pilot study of 30 patients based on a validated prediction rule.
Authors: Talcott J A , Whalen A , Clark J , Rieker P P , Finberg R 
Published: February 2017

PURPOSE To assess the feasibility of early discharge to home therapy with standard intravenous antibiotics in 30 patients with fever and neutropenia at low risk by a validated clinical decision rule. PATIENTS AND METHODS Newly admitted outpatients with fever and neutropenia were evaluated for home therapy during 2 days of inpatient observation. To evaluate enrolled patients' acceptance of home care, we assessed patient attitudes and quality of life before and after home therapy. To assess economic effects, we compared the medical charges of patients treated at home with those of medically eligible patients who remained in the hospital. RESULTS Of the first 84 patients, 50 (60%) were medically ineligible, and neutropenia was resolved in another eight (10%) during the observation period. Only nine patients of the remaining 26 who were medically eligible (35%) were enrolled in the home-therapy trial. Thereafter, 21 of 31 medically eligible patients (68%) were enrolled. The 30 patients treated at home were neutropenic for a median of 6 days (mean, 8.2). Four had medical complications, and five others were readmitted for observation. Patients' quality of life improved during home therapy, and favorable attitudes toward home care persisted after treatment. Medically eligible patients not enrolled had briefer neutropenia than patients treated at home, but had 44% higher daily medical charges and equivalent overall charges despite treatment half as long. CONCLUSION We conclude that early discharge of low-risk patients to home intravenous antibiotic therapy is feasible, is well received by patients, and may prove to be cost-saving. However, these conclusions must be validated in a large randomized trial.
MDR-1 expression and response to vincristine, doxorubicin, and dexamethasone chemotherapy in multiple myeloma refractory to alkylating agents.
Authors: Cornelissen J J , Sonneveld P , Schoester M , Raaijmakers H G , Nieuwenhuis H K , Dekker A W , Lokhorst H M 
Published: February 2017

PURPOSE To assess whether the presence of enhanced multiple drug resistance (MDR)-1 gene expression in multiple myeloma (MM) patients predicts survival, as well as response to vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy. PATIENTS AND METHODS Sixty-three MM patients refractory to alkylating therapy were studied. The presence of the MDR-1 gene product, a 170-kd glycoprotein (P-170), was analyzed in bone marrow plasma cells by means of the alkaline phosphatase (APAAP) technique using the P-170-specific monoclonal antibody (MoAb) C219. The prognostic value of MDR-1 gene expression, examined before VAD treatment, was compared with other established prognostic factors including beta 2-microglobulin, albumin, lactate dehydrogenase (LDH), and the plasma cell labeling index. RESULTS Fifty-nine percent of all samples were P-170-positive. No association could be demonstrated between response to VAD and MDR-1 gene expression (chi 2 P = .359), in contrast to high serum beta 2-microglobulin levels, which were positively correlated with response (P = .006). P-170-positive and -negative patients showed a median survival duration of 23 and 22 months, respectively, a difference that was not statistically significant (P = .9). beta 2-microglobulin, LDH, albumin, and the plasma cell labeling index were all significantly correlated with survival. CONCLUSION These results indicate that other mechanisms of resistance must be involved in MM apart from MDR. The role of MDR status at this stage of disease may be biased by the major contribution of dexamethasone to induction of response by VAD in MM patients.
Advanced seminoma: treatment results, survival, and prognostic factors in 142 patients.
Authors: Mencel P J , Motzer R J , Mazumdar M , Vlamis V , Bajorin D F , Bosl G J 
Published: February 2017

PURPOSE To investigate the efficacy of chemotherapy and to assess the relationship between selected pretreatment characteristics and survival in patients with advanced seminoma. PATIENTS AND METHODS One hundred forty-two patients with advanced seminoma treated with platinum-based chemotherapy were the subject of this study. Treatment regimens included cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6) (45 patients), a six-cycle regimen of VAB-6 alternating with etoposide and cisplatin (two patients), cisplatin and etoposide (60 patients), and etoposide and carboplatin (35 patients). RESULTS One hundred thirty of 140 (93%) assessable patients treated with platinum-based therapy achieved a favorable response (complete response or a partial response with negative serum tumor markers). One hundred twenty-five patients (88%) are alive and 120 (86%) remain progression-free at a median follow-up duration of 43 months. Fifty-seven of 60 patients (95%) who were treated with cisplatin and etoposide achieved a favorable response; 55 (92%) remain progression-free. The relative risks of death or of an event (death or relapse) related to human chorionic gonadotropin (HCG) elevation were 1.8 (P = .04) and 1.96 (P = .001), respectively. The relative risks of death or of an event associated with lactate dehydrogenase (LDH) elevation were 2.6 (P = .05) and 2.7 (P = .02), respectively. All 19 patients with a mediastinal primary tumor site achieved a complete response, and 18 of 19 (95%) remain progression-free. CONCLUSION Four cycles of cisplatin and etoposide is highly effective therapy for seminoma and is the standard therapy at our center. Elevation of the serum markers HCG and LDH were of prognostic significance, while an extragonadal primary tumor site was not associated with an adverse prognosis. Studies of tumor biology, including genetic analysis, are ongoing to determine other parameters that may correlate with response and survival.
Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer.
Authors: Buroker T R , O'Connell M J , Wieand H S , Krook J E , Gerstner J B , Mailliard J A , Schaefer P L , Levitt R , Kardinal C G , Gesme D H 
Published: February 2017

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.