bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer.
Authors: Jones S , Winer E , Vogel C , Laufman L , Hutchins L , O'Rourke M , Lembersky B , Budman D , Bigley J , Hohneker J 
Published: February 2017

PURPOSE This prospective multicenter randomized trial was performed to compare the effectiveness and safety of intravenous (i.v.) vinorelbine tartrate (Navelbine [NVB]; Burroughs Wellcome Co, Research Triangle Park, NC) with i.v. melphalan (Alkeran [ALK]; Burroughs Wellcome Co) in a heavily pretreated population of patients with anthracycline-refractory advanced breast cancer (ABC). Efficacy end points included time to disease progression (TDP), time to treatment failure (TTF), survival, tumor response rates, and quality of life (QL) and relief of cancer-related symptoms. PATIENTS AND METHODS Between August 24, 1990, and December 1, 1992, 183 patients were randomized (2:1) to treatment with NVB (30 mg/m2 weekly) or ALK (25 mg/m2 every 4 weeks) i.v. Patients were stratified by measurable or nonmeasurable-assessable disease and by treatment center. RESULTS Time to disease progression was significantly longer with NVB than with ALK, with a median 12 weeks versus 8 weeks, respectively (P < .001). NVB patients also had significantly longer time to treatment failure than ALK patients, with a median 12 weeks versus 8 weeks, respectively (P < .001). The effect of NVB on survival was also statistically significant (P = .034): 1-year survival rates were 35.7% with NVB and 21.7% with ALK and the median survival rate was 35 weeks and 31 weeks, respectively. In total, 46.5% of NVB patients and 28.2% of ALK patients achieved an objective response or stabilization of disease (P = .06). No intergroup differences were noted in patient-assessed QL and cancer-related symptoms. The most common toxicities were hematologic, including granulocytopenia with NVB and thrombocytopenia and granulocytopenia with ALK. Both drugs were generally well tolerated, and no septic deaths were reported. CONCLUSION This randomized trial demonstrates a survival benefit in anthracycline-refractory ABC. NVB was well tolerated and demonstrated activity superior to ALK in anthracycline-refractory ABC, without compromising QL. Based on activity of single-agent NVB in this difficult-to-treat patient population, investigations of NVB in combination with other anticancer drugs are warranted.
Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy.
Authors: Chi K H , Chen C H , Chan W K , Chow K C , Chen S Y , Yen S H , Chao J Y , Chang C Y , Chen K Y 
Published: February 2017

PURPOSE To evaluate prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the reduction of chemotherapy-induced oral mucositis. PATIENTS AND METHODS Twenty patients with stage IV squamous cell carcinoma of head and neck were studied. Two-cycles (periods) of identical doses of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) chemotherapy with cisplatin 20 mg/m2/d, 5-FU 800 mg/m2/d, leucovorin 90 mg/m2/d by 96-hour continuous intravenous infusion every 3 weeks were given to each patient. After PFL chemotherapy, GM-CSF 4 micrograms/kg subcutaneously from days 5 to 14 or no therapy was given by a randomized self-controlled crossover study design. Oral mucositis was graded with modified Radiation Therapy Oncology Group criteria. RESULTS In the first cycle of PFL chemotherapy, GM-CSF significantly reduced the incidence, mean duration, and mean area under the curve (AUC) of severe oral gross mucositis (grade > or = 3) compared with no therapy. These beneficial effects continued into the second cycle of PFL chemotherapy after crossover to no GM-CSF. The incidence of severe mucositis was reduced when GM-CSF was given in the second cycle of PFL. Analysis of variance indicated significant direct GM-CSF treatment effects on the mean AUC of gross/functional scores and duration of moderate gross mucositis (grade > or = 2) over both periods. There was a significant period effect in favor of giving GM-CSF in the first cycle of chemotherapy. CONCLUSION GM-CSF can significantly reduce the severity and duration of chemotherapy-induced oral mucositis after PFL chemotherapy.
Nonsteroidal antiinflammatory drugs for cancer pain: comparison between misoprostol and ranitidine in prevention of upper gastrointestinal damage.
Authors: Valentini M , Cannizzaro R , Poletti M , Bortolussi R , Fracasso A , Testa V , Sozzi M , Fornasarig M , Bortoluzzi F , Grazioli I 
Published: February 2017

PURPOSE The prophylactic strategy of nonsteroidal antiinflammatory drug (NSAID)-induced upper gastrointestinal (UGI) damage has largely been studied in arthritic patients, but not in cancer patients. The efficacy of misoprostol and ranitidine in the prevention of gastroduodenal damage in patients taking diclofenac for their cancer pain has been compared in this study. PATIENTS AND METHODS Patients who needed high-dose (200 to 300 mg/d) diclofenac for cancer pain and without mucosal lesions at baseline gastroduodenal endoscopy were randomized to receive misoprostol (200 micrograms twice daily; M group) or ranitidine (150 mg twice daily; R group). UGI endoscopy was repeated after 4 weeks. RESULTS Twenty-three patients treated with misoprostol and 26 treated with ranitidine concluded the study. The M group showed a significantly (P < .02) lower incidence of gastroduodenal lesions (two patients; 8.7%) than the R group (10 patients; 38.5%). Gastric ulcers occurred in one (4%) misoprostol-treated patient and in six (23%) ranitidine-treated patients. Six of seven patients with ulcers were asymptomatic. Seventy-one percent and 86% of ulcers occurred in patients older than 60 years and in those who received greater than 3.1 mg/kg of diclofenac, respectively. CONCLUSION Misoprostol was significantly more effective than ranitidine in the prevention of gastroduodenal lesions in cancer patients receiving diclofenac.
p53 Status predicts survival in breast cancer patients treated with or without postoperative radiotherapy: a novel hypothesis based on clinical findings.
Authors: Jansson T , Inganäs M , Sjögren S , Norberg T , Lindgren A , Holmberg L , Bergh J 
Published: February 2017

PURPOSE AND METHODS Primary breast cancer tumors without axillary metastases from 206 consecutive patients in a population-based cohort were investigated with regard to the presence of an intact p53 gene using a cDNA-based sequencing method. Clinical follow-up data and outcome of node-negative patients without any adjuvant systemic therapy (n = 168) were related to locoregional radiotherapy and p53 status. RESULTS Mutations in p53 occurred in 31 node-negative breast cancer patients who did not receive any systemic adjuvant treatment, but were treated with postoperative locoregional radiotherapy or nothing. Node-negative breast cancer patients with p53 mutations had significantly improved relapse-free survival (P = .0007), breast cancer-corrected survival (P = .01), and overall survival (P = .02) rates when treated with locoregional radiotherapy. In node-negative breast cancer patients with wild-type p53, there was no statistically significant difference in outcome between patients who received locoregional radiotherapy and those who did not. Cox proportional hazards models indicate that mutant p53 is associated with worse prognosis independent of response to radiotherapy and that response to radiotherapy is qualitatively different in tumors with p53 mutations compared with those with wild-type p53. CONCLUSION Our clinical findings define a group of breast cancer patients in whom locoregional radiotherapy improves relapse-free, breast cancer-corrected, and overall survival. The outcome for irradiated node-negative breast cancer patients with p53 alterations indicates that irradiation can induce cell death even in the presence of p53 mutations.
Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer.
Authors: Lise M , Nitti D , Marchet A , Sahmoud T , Buyse M , Duez N , Fiorentino M , Dos Santos J G , Labianca R , Rougier P 
Published: February 2017

PURPOSE In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.
Pediatric desmoid tumor: retrospective analysis of 63 cases.
Authors: Faulkner L B , Hajdu S I , Kher U , La Quaglia M , Exelby P R , Heller G , Wollner N 
Published: February 2017

PURPOSE This study was conducted to evaluate clinical prognostic factors predictive of the probability of recurrence of desmoid tumor (DT). PATIENTS AND METHODS Sixty-three patients with histologically confirmed diagnosis of DT were retrospectively studied. Median age at diagnosis was 13 years. Patient distribution by site was as follows: 61% extremities, 18% head and neck, 13% trunk (including 5% intraabdominal), and 8% multicentric lesions. All patients had partial or complete resections; 20 patients also received radiotherapy and/or chemotherapy. RESULTS At a median follow-up time of 6 years since first treatment, the overall actuarial probability of having one or more recurrences was 75%. Age, sex, site, size, or number of previous recurrences had no significant impact on the likelihood of recurrence. The only factor associated with an increased proportion of recurrence-free patients was a negative margin of resection (70% v 15% with positive margins; P = .006). Of the four patients with more than 3 years follow-up since chemotherapy, two recurred, and of the 11 patients with the same follow-up after radiotherapy, four recurred, including two of five patients who received a dose of 50 Gy or more. No deaths directly related to tumor invasion were observed. CONCLUSION A surgical approach aiming at clear margins is presently the best treatment option. When this cannot be accomplished without severe disfigurement or function impairment, partial resection is an acceptable alternative, but one associated with a high risk of regrowth. Whether adjuvant strategies should be used in this situation remains to be addressed.
High-dose CHOP as initial therapy for patients with poor-prognosis aggressive non-Hodgkin's lymphoma: a dose-finding pilot study.
Authors: Shipp M A , Neuberg D , Janicek M , Canellos G P , Shulman L N 
Published: February 2017

PURPOSE To purpose of this study was to develop a more effective approach to the treatment of patients with poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty newly diagnosed patients with bulky (> or = 10 cm) advanced-stage aggressive NHL were enrolled onto a pilot study. The study was designed to determine the maximum-tolerated dosages (MTD) of cyclophosphamide and doxorubicin that could be used in a high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with granulocyte colony-stimulating factor (G-CSF) support and to assess preliminarily the efficacy of the regimen. RESULTS In the initial dose-finding portion of the study, cumulative thrombocytopenia was the dose-limiting toxicity. At the MTD, the regimen included four 21-day cycles of cyclophosphamide 4 gm/m2, doxorubicin 70 mg/m2, vincristine 2 mg, and prednisone 100 mg for 5 days with mesna and G-CSF support. At the MTD, 65% of treatment cycles were complicated by febrile neutropenia, 84% of patients received at least one platelet transfusion for platelet counts less than 20,000/microL, and there was one treatment-related death. Nineteen of 22 (86%; 90% confidence interval [CI], 68 to 96) patients treated at the MTD achieved an initial complete response (CR), and 79% (90% CI, 58 to 92) of the complete responders and 69% of all patients remain progression-free with 20 months median follow-up. CONCLUSION The high-dose CHOP regimen may be an effective alternative for patients with poor-prognosis aggressive NHL.
Evaluation of prostate-specific antigen as a surrogate marker for response of hormone-refractory prostate cancer to suramin therapy.
Authors: Sridhara R , Eisenberger M A , Sinibaldi V J , Reyno L M , Egorin M J 
Published: February 2017

PURPOSE We evaluated the surrogate role of serum prostate-specific antigen (PSA) using prospectively collected information from patients with hormone-refractory prostate cancer (HRPC) treated with suramin. MATERIALS AND METHODS Data from 103 patients were analyzed using survival analysis, exploratory analysis, and regression analysis. RESULTS There was a significant survival difference between groups of patients with a PSA decrease of < or = 0% or greater than 0% (P = .018). There were no significant overall survival differences between groups of patients with PSA decreases less than 50% or > or = 50% and less than 75% or > or = 75%. Tree-based modeling did not define a specific threshold percentage PSA change as a response criterion. For a response of 1-year survival, sensitivity increased (0.91 v 0.69), but specificity decreased (0.37 v 0.62), with a 75% versus 50% PSA decrease used as classification criterion. Differences between the area under the receiver-operating curves (ROCs) with 50% and 75% PSA decreases as threshold values were small. For a response of 1-year survival, attributable proportions were 0.38 and 0.68, respectively, with 50% and 75% PSA decreases as threshold values. When pretreatment variables were assessed by Cox proportional hazards model, hemoglobin level was the most significant predictor of survival. When percentage PSA change was included in the model, hemoglobin level remained the most significant factor, but percentage PSA change was also a weak, but statistically significant, factor. PSA was a weak, but statistically significant, predictor of survival in Cox proportional hazards model with PSA as a time-variant covariate. CONCLUSION Reduction in PSA level has weak prognostic significance with respect to survival in HRPC patients, but, currently, PSA reduction cannot be used as a reliable response criterion to evaluate treatment efficacy in individual patients. Prospective, randomized studies, including prospective measurement of other indices related to symptomatic clinical benefits, are required.
An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia.
Authors: Ribeiro R C , Rivera G K , Hudson M , Mulhern R K , Hancock M L , Kun L , Mahmoud H , Sandlund J T , Crist W M , Pui C H 
Published: February 2017

PURPOSE To assess the salvage rate and long-term complications among children treated with an intensive regimen for isolated CNS relapse during first remission of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Twelve boys and eight girls, diagnosed at a median age of 4 years, had CNS relapse at a median age of 7 years. Five had CNS leukemia at presentation, while five completed treatment before relapse. First complete remission lasted a median of 22.5 months. Ten patients had received cranial irradiation plus intrathecal (IT) therapy, and the remainder had received high-dose intravenous and/or IT methotrexate (MTX) as CNS-directed treatment. Retrieval therapy consisted of a five-agent intensive reinduction regimen followed by continuation therapy with four rotating drug pairs. Triple-IT therapy was administered weekly for 4 to 5 weeks, then every 6 weeks until craniospinal radiation (cranium, 24 Gy; spine, 15 Gy; both sites, 1.5 Gy per fraction) was administered. RESULTS All 20 children achieved a second complete remission. The 5-year estimate of disease-free survival (mean +/- SE) was 70% +/- 11%. Thirteen patients remain in remission at 71+ to 126+ months (median, 104+), and 10 of 13 patients tested have normal IQ scores. Four patients have had a second relapse (one CNS and three non-CNS), and three have developed other malignancies. Prior cranial irradiation was associated with subsequent failure; only three of 10 patients who previously received radiotherapy, compared with all of the other 10 patients, remained in second remission. CONCLUSION This intensive retrieval therapy is effective and well tolerated by children with an isolated CNS relapse of ALL, especially those who have not received prior cranial irradiation. Most patients have no significant neuropsychologic impairment.
Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin.
Authors: Merrouche Y , Negrier S , Bain C , Combaret V , Mercatello A , Coronel B , Moskovtchenko J F , Tolstoshev P , Moen R , Philip T 
Published: February 2017

PURPOSE Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) has been reported to mediate tumor regression in some human cancers. To define better the biologic characteristics of TIL, especially survival and distribution in vivo, we performed a gene-marker study in patients with advanced malignancies. PATIENTS AND METHODS We treated five patients with metastatic melanoma or renal cell carcinoma with adoptive immunotherapy. TIL were genetically modified, before their infusion, using a recombinant retroviral vector that contained the marker gene coding for resistance to neomycin (NeoR). RESULTS All of the patients tolerated the treatment well and none of the theoretic safety hazards due to the retroviral gene transduction was observed. The presence of the NeoR gene in TIL was detected by Southern blot analysis, with an efficiency of transduction that ranged from 1% to 26%. With polymerase chain reaction (PCR) analysis, we demonstrated that gene-modified TIL can survive for several months after reinjection, since positive blood samples were observed up to day 260 following reinjection. Eight malignant biopsy specimens were obtained from three patients after cell infusion. TIL were detected in only four of these eight tumor deposits on days 7 and 260. CONCLUSION These results confirm the feasibility and safety of using in vitro retroviral gene transduction in human lymphocytes to analyze their in vivo distribution for further therapeutic applications. However, a selective and prolonged retention of TIL at the tumor site was not found in this study.
Influence of prior and subsequent pregnancy on breast cancer prognosis.
Authors: von Schoultz E , Johansson H , Wilking N , Rutqvist L E 
Published: February 2017

PURPOSE AND METHODS The prognostic influence of pregnancies 5 years before (n = 173) and after (n = 50) breast cancer diagnosis was investigated in 2,119 women less than 50 years of age with a primary operable breast cancer. The main end point was distant metastasis. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In the analyses of the effect of pregnancy after diagnosis of breast cancer, a Cox model with a time-dependent covariate was applied. RESULTS Women with a pregnancy before diagnosis had slightly larger tumors than the control group. However, they did not differ with respect to nodal status and estrogen receptor (ER) status. There was no evidence that women with a pregnancy during the 5-year period preceding breast cancer diagnosis had a worse prognosis compared with women without pregnancy during the same period. Similarly, there was no evidence that women with a pregnancy after breast cancer diagnosis had a worse prognosis. CONCLUSION The hormonal changes associated with pregnancy thus seem to have little, if any, influence on the prognosis of breast cancer. In the present study, at least, there was no indication of a worse prognosis. In fact, the relative hazard for women who became pregnant after diagnosis of breast cancer in comparison with women without a subsequent pregnancy was 0.48 (P = .14), which suggested a possible decreased risk of distant dissemination.
Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer.
Authors: Powles T J , Hickish T F , Makris A , Ashley S E , O'Brien M E , Tidy V A , Casey S , Nash A G , Sacks N , Cosgrove D 
Published: February 2017

PURPOSE To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.