bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein.
Authors: Yamauchi H , O'Neill A , Gelman R , Carney W , Tenney D Y , Hösch S , Hayes D F 
Published: February 2017

PURPOSE Overexpression of the HER-2/c-neu/c-erbB2 proto-oncogene is associated with a worse prognosis in patients with breast cancer, perhaps due to an association of the HER-2 proto-oncogene protein with resistance to hormone and/or chemotherapy. Circulating levels of the extracellular domain (ECD) of the HER-2/c-neu-related protein (NRP) are elevated in 20% to 40% of patients with metastatic breast cancer. We investigated whether pretreatment levels of NRP predict response to hormone therapy (HT). MATERIALS AND METHODS Circulating NRP levels were determined in 94 patients who participated in a randomized trial of three different doses of the antiestrogen, droloxifene (DRO), as first-line HT for metastatic breast cancer. RESULTS NRP levels were elevated (> or = 5,000 U/mL) in 32 of 94 patients (34%). Only three of 32 patients (9%) with elevated NRP levels responded to DRO, compared with 35 of 62 (56%) with nonelevated NRP levels (P = .00001). Low pretreatment NRP level was the most powerful predictor of response to DRO (odds ratio of response, 22.4; P = .0001). Elevated pretreatment NRP levels were also associated with a shorter time to progression (TTP) and survival duration. CONCLUSION Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT.
Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy.
Authors: Leyvraz S , Spataro V , Bauer J , Pampallona S , Salmon R , Dorval T , Meuli R , Gillet M , Lejeune F , Zografos L 
Published: February 2017

PURPOSE Ocular melanoma is characterized by a high rate of liver metastases and is associated with a median survival time less than 5 months. There is no standard treatment available. Treatment strategies have, without success, relied on the experience with metastatic cutaneous melanoma. The only effective treatment is chemoembolization using cisplatin and polyvinyl sponge, which has never become accepted on a large scale. The objective of the study was to establish prospectively the efficacy and toxicity of hepatic intraarterial fotemustine, a third-generation nitrosourea, in patients with liver metastases from ocular melanoma. PATIENTS AND METHODS Thirty-one patients were subjected to laparotomy to place a totally implantable catheter into the hepatic artery and received fotemustine 100 mg/m2 as a 4-hour infusion, first once a week for four times and then, after a 5-week rest period, every 3 weeks until progression or toxicity. Cox regression models were used to assess the prognostic role of patient survival characteristics. RESULTS Objective responses were observed in 12 of 30 assessable patients (40%; 95% confidence interval, 22% to 59%). The median duration of response was 11 months and the median overall survival time, 14 months. Lactate dehydrogenase (LDH) appeared to be the strongest prognostic factor for survival. Toxicity was minimal and treatment could be administered on an outpatient basis. CONCLUSION The results of hepatic arterial chemotherapy with fotemustine produced a high response rate and survival similar to chemoembolization therapy. It involves no major toxicity and preserves the quality of life. To assess further its effectiveness, a randomized study to compare hepatic intraarterial versus intravenous chemotherapy is being planned.
Phase II study of continuous infusion carmustine and cisplatin followed by cranial irradiation in adults with newly diagnosed high-grade astrocytoma.
Authors: Grossman S A , Wharam M , Sheidler V , Kleinberg L , Zeltzman M , Yue N , Piantadosi S 
Published: February 2017

PURPOSE To evaluate the activity and toxicity of carmustine (BCNU) and cisplatin administered as a 72-hour continuous intravenous infusion before radiation in adults with newly diagnosed high-grade astrocytomas. PATIENTS AND METHODS Fifty-two patients with a Karnofsky performance status greater than 60 and no prior antineoplastic therapy entered this protocol. The median age of the patients was 55 years. Eighty-eight percent had glioblastoma multiforme and 12% had anaplastic astrocytomas. BCNU (40 mg/m2/d) and cisplatin (40 mg/m2/d) were administered concurrently as a 72-hour infusion every 3 to 4 weeks. Radiation was begun 4 weeks after the third cycle of chemotherapy or earlier for progressive disease. Responses required a > or = 50% reduction in contrast-enhancing volume. RESULTS Forty patients (77%) completed three chemotherapy infusions, five (10%) received two infusions, and seven (13%) received only one. Fifty-one patients completed radiation. Seventeen (42%) patients with measurable disease had a partial response (PR) to chemotherapy, 23 (53%) had stable disease (SD), and two (4%) had progressive disease (PD) on chemotherapy. The median survival time for all patients was 13 months. Survival rates at 1, 2, 3, and 5 years were 62%, 19%, 12%, and 5%, respectively. Grade III to IV leukopenia occurred in 32% of patients; 63% received platelet transfusions and 58% required RBCs. Neutropenic fevers were rare and no intracranial hemorrhages or treatment-related deaths were noted. Nausea, vomiting, peripheral neuropathy, hearing loss, and thromboembolic events were relatively common. CONCLUSION This chemotherapy regimen appears to have significant activity and may prolong survival in adults with newly diagnosed high-grade astrocytoma.
Treatment of T-cell prolymphocytic leukemia with human CD52 antibody.
Authors: Pawson R , Dyer M J , Barge R , Matutes E , Thornton P D , Emmett E , Kluin-Nelemans J C , Fibbe W E , Willemze R , Catovsky D 
Published: February 2017

PURPOSE T-prolymphocytic leukemia (T-PLL) is an aggressive malignancy of mature T cells refractory to conventional chemotherapy, with a median survival duration of 7.5 months. We report here promising results with the use of a genetically reshaped human CD52 antibody, CAMPATH-1H. PATIENTS AND METHODS Fifteen patients with T-PLL, most of whom had received the purine analog deoxycoformycin (DCF), were treated with CAMPATH-1H. Results were compared with those of 25 patients treated with DCF. RESULTS Major responses occurred in 11 patients (73%) treated with CAMPATH-1H compared with 40% with DCF. Complete remissions (CRs) were documented in nine (60%) of the CAMPATH-1H cases and only three (12%) were obtained with DCF. CRs with CAMPATH-1H were durable, and re-treatment with the antibody resulted in second CRs in three relapsed patients. Two of them were successfully autografted with peripheral-blood and bone marrow stem cells collected during the first CR. Apart from first-dose reactions, infusions of CAMPATH-1H were well tolerated. However, two responding patients developed severe bone marrow aplasia that was fatal in one; the second remained moderately pancytopenic 21 weeks after stopping CAMPATH-1H therapy. The cause of this adverse effect is unknown. CONCLUSION CAMPATH-1H is an effective agent in T-PLL and represents a significant improvement over other types of therapy. However, CAMPATH-1H alone is not sufficient for long-term remissions, and the role of autologous stem-cell transplantation needs further investigation.
Brain tumor-polyposis syndrome: two genetic diseases?
Authors: Paraf F , Jothy S , Van Meir E G 
Published: February 2017

PURPOSE AND DESIGN This report presents a comprehensive and statistical analysis of the brain tumor-polyposis (BTP) cases referred to as Turcot's syndrome in the literature. RESULTS BTP patients encompass a heterogeneous group that can be classified into two statistically distinct clinical entities based on phenotype of the polyps (P = .0001), presence of colorectal cancer (P = .0001), type of brain neoplasm, ie, glioma or medulloblastoma (P = .0001), presence of skin lesions (P = .0004) and cafe-au-lait spots (P = .0008), as well as consanguinity (P = .0135). CONCLUSION The first entity (BTP syndrome type 1) consists of patients who have glioma and colorectal adenomas without polyposis (non-FAP cases), and their siblings with glioma and/or colorectal adenomas. For these patients, we show that the patient's age at malignant glioma occurrence is less than 20 years (50 to 80 years in the general population), which strongly supports the existence of an underlying genetic cause. The neoplasms of these patients show DNA replication errors, which suggests a relationship with hereditary nonpolyposis colorectal cancer (HNPCC), a disease characterized by germline alterations in DNA mismatch repair genes. The second entity (BTP syndrome type 2) consists of patients with a CNS tumor that occurs in a familial adenomatous polyposis kindred (FAP cases). These patients carry germline mutations in the APC gene, which suggests that mutations in this gene might predispose to brain tumors. Risk analysis shows increased incidence of medulloblastoma in FAP patients, but APC mutations are not found in sporadic glioma or medulloblastoma. Therefore, further investigations should establish whether the occurrence of medulloblastoma in an FAP family represents a variant of FAP.
Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study.
Authors: Weiner M A , Leventhal B , Brecher M L , Marcus R B , Cantor A , Gieser P W , Ternberg J L , Behm F G , Wharam M D , Chauvenet A R 
Published: February 2017

PURPOSE To determine whether the addition of low-dose total-nodal irradiation (TNI) in pediatric patients with advanced-stage Hodgkin's disease who have received eight cycles of alternating mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) will improve the event-free survival (EFS) and overall survival (OS) when compared with patients who have received chemotherapy only. PATIENTS AND METHODS At diagnosis, 183 children and adolescents with stages IIB, IIIA2, IIIB, and IV Hodgkin's disease were randomized to receive eight cycles of alternating MOPP-ABVD with or without low-dose TNI. RESULTS Of 183 patients, four were rendered ineligible before treatment was initiated. One hundred sixty-one of 179 patients (90%) were in complete remission (CR) at the completion of eight cycles of alternating MOPP-ABVD; 81 were in the chemotherapy-only group and proceeded to observation off therapy, whereas 80 of 161 were to receive combined modality therapy (CMT). Nine of 80 patients randomized at the time of diagnosis to receive CMT did not receive radiation (RT) because of a protocol violation, but were monitored for EFS and OS and included in all analyses. The estimated EFS and OS rates at 5 years for the 179 eligible patients are 79% and 92%, respectively. The actuarial EFS at 5 years was 80% for patients who received CMT and 79% for patients who received MOPP-ABVD only. The OS for the former group is estimated to be 87% and for the latter patients 96%. Age < or = 13 years of age at diagnosis and the attainment of a clinical CR after three cycles of chemotherapy were associated with a statistically significant improved EFS. CONCLUSION Our results indicate that after the delivery of eight cycles of MOPP-ABVD, the addition of low-dose RT does not improve the estimated EFS or OS in pediatric patients with advanced-stage Hodgkin's disease.
Effect of amifostine on toxicities associated with sequential chemotherapy and radiation therapy for unresectable non-small-cell lung cancer: results of a phase II trial.
Authors: Tannehill S P , Mehta M P , Larson M , Storer B , Pellet J , Kinsella T J , Schiller J H 
Published: February 2017

PURPOSE To determine the effect of amifostine on the safety and efficacy of induction chemotherapy with high-dose cisplatin and vinblastine followed by large-field thoracic irradiation to 60 Gy in patients with stage IIIA or IIIB non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Twenty-six patients with unresectable stage IIIA or IIIB NSCLC were entered onto the study between May 1991 and November 1994. Patients received amifostine (740 or 910 mg/m2) followed by cisplatin (120 mg/m2) on days 1 and 29. Vinblastine (5 mg/m2) was given weekly for 5 weeks with no amifostine pretreatment. Following chemotherapy, patients received amifostine (340 mg/m2 4 days a week for 5 weeks, or 200 mg/m2 5 days a week for 6 weeks) 15 minutes before definitive thoracic radiation therapy to a total dose of 60 Gy in 6 weeks. RESULTS Twenty-five patients were assessable for response and survival. The objective response rate was 60%. One-, 2-, and 3-year survival rates were 55%, 23%, and 23%. There was no grade 3 or greater renal toxicity during chemotherapy or grade 3 or greater esophagitis during radiation therapy. Neutropenia (secondary to vinblastine use) was the only grade 4 toxicity. There were no treatment-related deaths. CONCLUSION Amifostine can be administered safely with high-dose cisplatin, vinblastine, and radiation therapy for NSCLC. The response rate and survival data provide no evidence that amifostine impairs response to treatment. Amifostine appears to reduce cisplatin-related nephrotoxicity and radiation-induced esophagitis.
HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas.
Authors: Press M F , Bernstein L , Thomas P A , Meisner L F , Zhou J Y , Ma Y , Hung G , Robinson R A , Harris C , El-Naggar A , Slamon D J , Phillips R N , Ross J S , Wolman S R , Flom K J 
Published: February 2017

PURPOSE The HER-2/neu gene codes for a membrane receptor protein that is homologous, but distinct from the epidermal growth factor receptor. This investigation was performed to validate fluorescence in situ hybridization (FISH) as a sensitive and specific method for assessing HER-2/neu gene amplification in archival tissue and to test whether this alteration is associated with poor prognosis. MATERIALS AND METHODS HER-2/neu gene amplification was determined by FISH in 140 archival breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node-negative breast cancers was assessed for amplification by FISH to determine the utility of HER-2/neu gene amplification. RESULTS Relative to solid-matrix blotting procedures, FISH analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers. Among patients treated by surgery only, the relative risks (relative hazard) of early recurrence (recurrent disease within 24 months of diagnosis), recurrent disease (at any time), and disease-related death were statistically significantly associated with amplification. The prognostic information contributed by HER-2/neu amplification was independent of the other markers studied. CONCLUSION FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification in the absence of adjuvant therapy is an independent predictor of poor clinical outcome and is a stronger discriminant than tumor size. Women with small tumors that had gene amplification were at increased risk of recurrence and disease-related death.
Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma.
Authors: Pazdur R , Diaz-Canton E , Ballard W P , Bradof J E , Graham S , Arbuck S G , Abbruzzese J L , Winn R 
Published: February 2017

PURPOSE The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses. RESULTS Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks. CONCLUSION At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.
Clinical impact of chemotherapy dose escalation in patients with hematologic malignancies and solid tumors.
Authors: Savarese D M , Hsieh C , Stewart F M 
Published: February 2017

PURPOSE To review published controlled clinical trials examining the benefit of escalated chemotherapy in patients with hematologic and solid malignancies. METHODS Studies were obtained by searching Medline and CancerLit and by review of bibliographies of published trials. We reviewed studies that examined dose-intense (DI) chemotherapy alone, in combination with hematopoietic colony-stimulating factors (CSFs), or high-dose therapy (HDT) with autologous bone marrow support (ABMT). RESULTS DI therapy without CSF or ABMT has not been shown to improve overall outcome in any tumor except consolidative therapy of acute myelogenous leukemia (AML). In solid tumors, many published studies suggest that less than standard-intensity chemotherapy is suboptimal, but few studies that examined higher compared with standard-dose therapy have shown a significant difference in outcome. No studies have convincingly demonstrated improved overall survival (OS) with DI therapy with CSF support. The use of HDT with ABMT has been shown to improve survival in multiple myeloma (MM), as well as relapsed intermediate- and high-grade non-Hodgkin's lymphoma (NHL). High-dose chemotherapy with ABMT is promising in patients with metastatic breast cancer (MBC), but it should not yet be considered a standard approach for these patients. CONCLUSION DI chemotherapy is an acceptable and standard therapeutic maneuver for patients with AML in first remission, MM, and relapsed aggressive NHL. In solid tumors, the use of DI chemotherapy either alone or with cytokine support has not been shown to improve outcome and should not be considered standard therapy. Current randomized trials should provide definitive answers about the role of DI therapy in solid tumors.
Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for squamous cell carcinoma of the head and neck: long-term results.
Authors: Clark J R , Busse P M , Norris C M , Andersen J W , Dreyfuss A I , Rossi R M , Poulin M D , Colevas A D , Tishler R B , Costello R , Lucarini J W , Lucarini D , Thornhill L , Lackey M , Peters E , Posner M R 
Published: February 2017

PURPOSE A phase II trial of cisplatin, fluorouracil, and leucovorin (PFL) induction chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck region (HNCA). PATIENTS AND METHODS One hundred two patients (stage III/IV, previously untreated) were treated with induction PFL. Patients with resectable primary tumor site lesions and clinical complete response (CR) were offered radiotherapy (RT) without surgery to the primary tumor site. Response, toxicity, local-regional therapy, survival, and preservation of the primary tumor site were assessed. RESULTS Among 279 courses, the overall response rate was 81%. Nineteen (19%) failed to respond, including three who died during therapy. Sixty-seven (69%) of 97 with assessable primary lesions had a clinical CR at the primary tumor site. Pathologic CR was recorded in 46 of 55 (84%) clinical CR patients who had biopsies performed on the primary tumor site. Toxicities resulted in unexpected hospitalizations in 19% of cases. After definitive local-regional therapy, 84 (82%) were disease-free including 71 (69%) with preserved primary tumor site anatomy. With a median follow-up time of 63 months, the cause-specific, overall (OS), and failure-free survival (FFS) rates at 5 years are 58%, 52%, and 51%. Local failure occurred in 29 of 102 (29%) and the local control rate at 5 years was 68%. CONCLUSION PFL has significant activity with acceptable toxicity in patients with advanced disease who have a good performance status. Preservation of the primary tumor site could be achieved without apparent loss of local control or survival. Management of neck disease by surgery or RT must be individualized and separate from management of primary tumor. Survival compares favorably with similar trials of induction chemotherapy or chemoradiotherapy.