bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Multicenter Phase II Trial of Oxaliplatin Plus Irinotecan Versus Raltitrexed as First-Line Treatment in Advanced Colorectal Cancer
Authors: Scheithauer Werner , Kornek Gabriela V. , Raderer Markus , Ulrich-Pur Herbert , Fiebiger Wolfgang , Gedlicka Claudia , Schüll Birgit , Brugger Stefan , Schneeweiss Bruno , Lang Fritz , Lenauer Alfred , Depisch Dieter 
Published: February 2017

PURPOSE: Irinotecan and oxaliplatin are two new agents with promising activity in advanced colorectal cancer. Based on preclinical and clinical evidence that both drugs act synergistically, a randomized phase II study was initiated to investigate the therapeutic potential and tolerance of this combination in the front-line setting. PATIENTS AND METHODS: Ninety-two patients with previously untreated, measurable disease were randomized to receive biweekly oxaliplatin 85 mg/m2 plus irinotecan 175 mg/m2 or raltitrexed 3 mg/m2 given on day 1 every 3 weeks. Upon development of progressive disease, second-line treatment with the opposite arm was effected. RESULTS: Patients allocated to oxaliplatin/irinotecan had a significantly better radiologically confirmed response rate (43.5% v 19.6%; P = .0025) and longer progression-free survival (median, 7.1 v 5.0 months; P = .0033). Improvement in overall survival, however, did not reach the level of significance (median, 16.0 v 16.5 months; P = .3943). The response rate after cross-over was 33.3% (eight of 24) for assessable patients treated with oxaliplatin/irinotecan compared with 14.2% (three of 21) for those treated with second-line raltitrexed. Oxaliplatin/irinotecan caused more hematologic and gastrointestinal toxicities, necessitating dose reductions in 10 of the first 20 patients. After adjustment of the irinotecan starting dose from 175 to 150 mg/m2, tolerance of treatment was acceptable; the most commonly encountered events (all grades) were neutropenia (81%), alopecia (65%), nausea/emesis (62%), peripheral sensory neuropathy (62%), and diarrhea (46%). CONCLUSION: Oxaliplatin/irinotecan seems beneficial as first-line therapy in advanced colorectal cancer, with an acceptable toxicity profile at the reduced irinotecan dose level. Its promising therapeutic potential is supported by the high response activity noted in the raltitrexed control arm after cross-over, which may also explain the lack of a difference in overall survival.
Variations in the Use of Chemotherapy for Elderly Patients With Advanced Ovarian Cancer: A Population-Based Study
Authors: Sundararajan Vijaya , Hershman Dawn , Grann Victor R. , Jacobson Judith S. , Neugut Alfred I. 
Published: February 2017

PURPOSE: Since 1986, the recommended therapy for patients with ovarian cancer has included surgery and chemotherapy with a platinum compound (cisplatin or carboplatin). The purpose of this study is to assess the use of chemotherapy in elderly patients with advanced ovarian cancer. METHODS: The Surveillance, Epidemiology, and End Results–Medicare database represents approximately 14% of the United States population and provides clinical and demographic information on cancer patients covered by Medicare, along with health care–utilization data from Medicare claims files. We analyzed the association of demographic and clinical factors with treatment among patients diagnosed from 1992 to 1996 with stage III or IV ovarian cancer, who survived ≥ 120 days beyond diagnosis, and were ≥ 65 years of age (N = 1,775). RESULTS: Approximately 83% of elderly patients received some form of chemotherapy within 4 months of diagnosis. In a multiple logistic regression model with patients aged 65 to 69 years as the reference, the odds ratios of receiving chemotherapy were 0.96 (95% confidence interval [CI], 0.63 to 1.46) for ages 70 to 74, 0.65 (95% CI, 0.43 to 1.00) for 75 to 79, 0.24 (95% CI, 0.15 to 0.37) for 80 to 84, and 0.12 (95% CI, 0.07 to 0.19) for 85+. Hispanic patients were less likely to receive chemotherapy than non-Hispanic white patients. Since 1992, paclitaxel has gradually replaced cyclophosphamide as the drug most commonly used with platinum. CONCLUSION: Despite its proven efficacy in treating ovarian cancer, chemotherapy seems to be used less among patients over age 65, especially those who are nonwhite and/or in the oldest age groups. Further research is needed to elucidate to what degree this represents appropriate clinical judgment and to what degree other factors, such as patient choice, play a role.
Neoadjuvant Chemotherapy and Radical Surgery Versus Exclusive Radiotherapy in Locally Advanced Squamous Cell Cervical Cancer: Results From the Italian Multicenter Randomized Study
Authors: Benedetti-Panici Pierluigi , Greggi Stefano , Colombo Alessandro , Amoroso Mariangela , Smaniotto Daniela , Giannarelli Diana , Amunni Gianni , Raspagliesi Francesco , Zola Paolo , Mangioni Costantino , Landoni Fabio 
Published: February 2017

PURPOSE: Neoadjuvant chemotherapy (NACT) and radical surgery (RS) have emerged as a possible alternative to conventional radiation therapy (RT) in locally advanced cervical carcinoma. In 1990, a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity. PATIENTS AND METHODS: Patients with squamous cell, International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study. They received cisplatin-based NACT followed by RS (type III to V radical hysterectomy plus systematic pelvic lymphadenectomy) (arm A) or external-beam RT (45 to 50 Gy) followed by brachyradiotherapy (20 to 30 Gy) (arm B). RESULTS: Of 441 patients randomly assigned to NACT+RS or RT, eligibility was confirmed in 210 and 199 patients, respectively. Treatment was administered according to protocol in 76% of arm A patients and 72% of arm B patients. Adjuvant treatment was delivered in 48 operated patients (29%). There was no evidence for any significant excess of severe morbidity in one of the two arms. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 58.9% and 55.4% for arm A and 44.5% and 41.3% for arm B (P = .007 and P = .02), respectively. Subgroup survival analysis shows OS and PFS rates of 64.7% and 59.7% (stage IB2-IIB, NACT+RS), 46.4% and 46.7% (stage IB2-IIB, RT) (P = .005 andP = .02), 41.6% and 41.9% (stage III, NCAT+RS), 36.7% and 36.4% (stage III, RT) (P = .36 and P = .29), respectively. Treatment had a significant impact on OS and PFS. CONCLUSION: Although significant only for the stage IB2 to IIB group, a survival benefit seems to be associated with the NACT+RS compared with conventional RT.
New Prognostic Score Based on Treatment Outcome of Patients With Relapsed Hodgkin’s Lymphoma Registered in the Database of the German Hodgkin’s Lymphoma Study Group
Authors: Josting Andreas , Franklin Jeremy , May Michael , Koch Peter , Beykirch Maria K. , Heinz Juergen , Rudolph Christian , Diehl Volker , Engert Andreas 
Published: February 2017

PURPOSE: To evaluate salvage treatment outcome of patients with relapsed Hodgkin’s disease (HD) and to distinguish different risk groups using identified prognostic factors.
PATIENTS AND METHODS: From 4,754 patients registered in the German Hodgkin’s Lymphoma Study Group (GHSG) database between 1988 and 1999, 422 patients with early (n = 170) or late (n = 252) relapsed HD were identified. One hundred seven patients (25%) relapsed after radiotherapy (RT) for early stages, 133 patients (32%) after combined-modality therapy for intermediate stages, and 182 patients (43%) after chemotherapy (CT) and RT to initial bulky disease or residual lymphoma for advanced stages. At relapse, characteristics of these 422 patients (median age, 38 years; range, 17 to 77) were stage III/IV, 45%; B symptoms, 24%; elevated erythrocyte sedimentation rate, 29%; anemia, 13%; and Karnofsky performance score, less than 90 in 13%. At first relapse, salvage treatment was RT in 13%, CT in 54%, and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) in 33%.
RESULTS: Median follow-up time after relapse was 45 months. Freedom from second failure (FF2F) and overall survival (OS) were 81% and 89% for relapse after RT, 33% and 46% for early relapse after CT, and 43% and 71% for late relapse after CT, respectively. In multivariate analysis, independent risk factors were time to relapse, clinical stage at relapse, and anemia at relapse. Four subgroups with significantly different FF2F and OS were identified. The prognostic score was predictive for patients who relapsed after RT, CT with conventional CT salvage, and CT with HDCT/ASCT.
CONCLUSION: In the GHSG database, time to relapse and clinical stage and anemia at relapse are relevant factors and can be used to form a prognostic score for HD patients at relapse.
Importance of Radiotherapy in the Outcome of Patients With Primary CNS Lymphoma: An Analysis of the CHOD/BVAM Regimen Followed by Two Different Radiotherapy Treatments
Authors: Bessell E. M. , López-Guillermo A. , Villá S. , Verger E. , Nomdedeu B. , Petit J. , Byrne P. , Montserrat E. , Graus F. 
Published: February 2017

PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P = .01). The 5-year overall survival (OS) was 36%. Age (< 60 v ≥ 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P = .04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.
Preoperative Chemotherapy Followed by Surgery Compared With Primary Surgery in Resectable Stage I (Except T1N0), II, and IIIa Non–Small-Cell Lung Cancer
Authors: Depierre Alain , Milleron Bernard , Moro-Sibilot Denis , Chevret Sylvie , Quoix Elisabeth , Lebeau Bernard , Braun Denis , Breton Jean-Luc , Lemarié Etienne , Gouva Sylvie , Paillot Nadine , Bréchot Jeanne-Marie , Janicot Henri , Lebas François-Xavier , Terrioux Philippe , Clavier Jean , Foucher Pascal , Monchâtre Michel , Coëtmeur Daniel , Level Marie-Claude , Leclerc Pascal , Blanchon François , Rodier Jean-Michel , Thiberville Luc , Villeneuve Anne , Westeel Virginie , Chastang Claude ,   from the French Thoracic Cooperative Group
Published: February 2017

PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m2, day 1), ifosfamide (1.5 g/m2, days 1 to 3) and cisplatin (30 mg/m2, days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P = .38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P = .15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P = .027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P = .044). Disease-free survival time was significantly longer in the PCT arm (P = .033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.
Palliative Uses of Methylphenidate in Patients With Cancer: A Review
Authors: Rozans Mark , Dreisbach Albert , Lertora Juan J.L. , Kahn Marc J. 
Published: February 2017

PURPOSE: Cancer is, unfortunately, often a terminal disease. The goal of therapy for many patients with cancer is palliation of symptoms common at the end of life, including pain, depression, and cognitive dysfunction. Methylphenidate is a psychostimulant most commonly used in the treatment of attention deficit hyperactivity disorder. In this report, we review the use of methylphenidate in the palliative care of patients with cancer.
METHODS: This review was written on the basis of a computerized literature search of Medline. We considered all English language publications from 1966 to present using the following key words: methylphenidate, palliative care, and cancer. Forty-nine articles were identified as being relevant for this review.
RESULTS: On the basis of this review, we came to the conclusion that methylphenidate is used to ameliorate opioid-induced somnolence, to augment the analgesic effects of opioids, to treat depression, and to improve cognitive function in patients with cancer.
CONCLUSION: The medical literature supports the palliative use of methylphenidate in the care of patients with cancer. Further placebo-controlled trials are needed to elucidate the precise role that methylphenidate will have in providing symptom relief to dying patients.
Survey of Modalities of Toxicity Assessment and Reporting in Noncomparative Prospective Studies of Chemotherapy in Breast Cancer
Authors: Perrone Francesco , De Maio Ermelinda , Maione Paolo , Di Maio Massimo , Ottaiano Alessandro , Pensabene Matilde , Di Lorenzo Giuseppe , Vernaglia Lombardi Alessandra , Gallo Ciro 
Published: February 2017

PURPOSE: To review how toxicity, a main end point of phase II studies, is assessed and reported in published phase II chemotherapy trials in breast cancer. METHODS: A survey was performed by hand-searching studies published in seven distinguished journals between 1995 and 1999. All selected articles were independently evaluated by two investigators using an ad hoc study report form. Descriptive statistics, contingency tables, and the χ2 test were applied. RESULTS: Overall, 122 articles were found; 65.6% lacked a statistical study design. Planned modalities for assessment of toxicity were inadequately reported in 20.5% of the studies. The scheduling of assessment of hematologic toxicity varied greatly. Toxicity was predominantly summarized per patient (69.7%). Although overall the World Health Organization scale was adopted more frequently (45.9%), the Common Toxicity Criteria (in different versions) were used more frequently in studies published in journals with a high impact factor (P = .001), in more recently initiated studies (P = .03), in sponsored studies (P = .0006), and in studies with an identifiable statistical design (P = .006). CONCLUSION: The wide diversity in modalities of toxicity assessment and reporting observed in this study suggests that the reliability of the body of published data on the toxicity of chemotherapy in breast cancer may be questionable. Current standards should be revised and harmonized to improve the reliability of such data. A checklist is proposed to help editorial evaluation of assessment and reporting of toxicity in phase II studies.
Reinfusion of Autologous Lymphocytes With Granulocyte-Macrophage Colony-Stimulating Factor Induces Rapid Recovery of CD4+ and CD8+ T Cells After High-Dose Chemotherapy for Metastatic Breast Cancer
Authors: de Gast G. C. , Vyth-Dreese F. A. , Nooijen W. , van den Bogaard C. J.C. , Sein J. , Holtkamp M. M.J. , Linthorst G. A.M. , Baars J. W. , Schornagel J. H. , Rodenhuis S. 
Published: February 2017

PURPOSE: Repeated high-dose chemotherapy (HDCT) followed by peripheral-blood progenitor cell (PBPC) transplantation can induce a complete remission in patients with metastatic breast cancer sensitive to standard chemotherapy (CT), but the majority of patients relapse within 1 to 2 years. The immune system is seriously compromised after HDCT, which precludes the development of effective immunotherapy. We investigated whether autologous lymphocytes, reinfused after HDCT, could induce a rapid recovery of T cells. PATIENTS AND METHODS: Three patients were monitored for immune recovery without reinfusion of lymphocytes. In the next 11 patients, stem cells were harvested after CT + granulocyte colony-stimulating factor (G-CSF) and lymphocytes were harvested after CT + granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2. These patients received stem cells and G-CSF after the first HDCT; stem cells, G-CSF, and lymphocytes after the second; and stem cells, GM-CSF, and lymphocytes after the third HDCT. RESULTS: Patients not receiving lymphocyte reinfusion had a very slow recovery of lymphocytes. In particular, CD4 counts remained low (< 200/μL for 9 months). Lymphocyte reinfusion had a significant effect on the recovery of lymphocytes, T cells, and CD8+ T cells (normalized on day 25). Recovery of CD4+ T cells was significantly accelerated by lymphocyte reinfusion and GM-CSF, leading to counts of 500/μL at 25 days. CONCLUSION: Lymphocyte reinfusion with G-CSF had a significant effect on the recovery of CD8+ T cells, whereas rapid recovery of CD4+ T cells required lymphocyte reinfusion and GM-CSF, which possibly acts as a survival factor through activation of antigen presenting cells. Whether the rapid recovery of CD4+ and CD8+ T cells prevents or delays relapse of the disease should be further investigated.
Phase I Study of Combination Topotecan and Carboplatin in Pediatric Solid Tumors
Authors: Athale Uma H. , Stewart Clinton , Kuttesch John F. , Moghrabi Albert , Meyer William , Pratt Charles , Gajjar Amar , Heideman Richard L. 
Published: February 2017

PURPOSE: We conducted a phase I trial of escalating doses of topotecan (TOPO) in association with a fixed systemic exposure of carboplatin (CARBO) with or without granulocyte colony-stimulating factor (G-CSF) in children. PATIENTS AND METHODS: Two separate cohorts of patients (pts) with solid tumors were studied: (A) pts with refractory or recurrent disease and (B) pts with no prior myelosuppressive therapy or newly diagnosed tumors for which there was no standard chemotherapy. CARBO was given on day 1 at an area under the curve of 6.5, followed by TOPO as a continuous infusion for 3 days; the starting dose of TOPO was 0.50 mg/m2/d. Cycles were repeated every 21 days. G-CSF was given at a dose of 5 μg/kg/d starting on day 4. RESULTS: Forty-eight of 51 pts were assessable for toxicity. In group A, dose-limiting myelosuppression persisted despite de-escalation of TOPO to 0.3 mg/m2/d and use of G-CSF. In group B, the maximum-tolerated dose of TOPO was 0.5 mg/m2/d for 3 days, and 0.6 mg/m2/d for 3 days with G-CSF. No significant nonhematologic toxicities were observed. Among 46 pts assessable for response, one had complete response, five had partial response, and 18 had stable disease. CONCLUSION: Although this combination possesses antineoplastic activity in pediatric solid tumors, hematologic toxicity precluded any meaningful TOPO dose escalation. The addition of G-CSF did not alter this. The potential for preservation of activity and diminution of toxicity with alternative sequences and schedules of administration (topoisomerase followed by alkylating or platinating agents) should be evaluated.
Value of Positron Emission Tomography With [F-18]Fluorodeoxyglucose in Patients With Colorectal Liver Metastases: A Prospective Study
Authors: Ruers T.J.M. , Langenhoff B.S. , Neeleman N. , Jager G. J. , Strijk S. , Wobbes Th. , Corstens F. H.M. , Oyen W. J.G. 
Published: February 2017

PURPOSE: To assess prospectively the value of fluor-18-deoxyglucose (FDG) positron emission tomography (PET), in addition to conventional diagnostic methods (CDM), as a staging modality in candidates for resection of colorectal liver metastases. PATIENTS AND METHODS: In 51 patients analyzed for resection of colorectal liver metastases, clinical management decisions were recorded after a complete work-up with CDM. Afterward, FDG-PET scans were performed and any change of clinical management according to FDG-PET results was carefully documented. Discordances between FDG-PET and CDM results were identified and related to the final diagnosis by histopathology, intraoperative findings, and follow-up. RESULTS: In 10 (20%) out of 51 patients, clinical management decisions based on CDM were changed after FDG-PET findings were known. FDG-PET detected unresectable pulmonary (n = 5) and hepatic metastases (n = 1) and ruled out extrahepatic (n = 2) and hepatic disease (n = 2). Due to FDG-PET, eight patients were spared unwarranted liver resection or laparotomy and two other patients were identified as candidates for liver resection. When the results of FDG-PET were regarded as decisive in a retrospective analysis, potential change of management was 29% (15 patients). FDG-PET and CDM showed discordant extrahepatic results in 11 patients (22%) and discordant hepatic results in eight patients (16%). Compared with CDM, FDG-PET resulted in true upstaging (n = 11), true downstaging (n = 5), false upstaging (n = 1), and false downstaging (n = 2). The detection rate of liver metastases on a lesion basis was generally better for computed tomography than for FDG-PET (80% v 65%); this was related to tumor size. CONCLUSION: FDG-PET as a complementary staging method improves the therapeutic management of patients with colorectal liver metastases, especially by detecting unsuspected extrahepatic disease.