bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereotactic radiosurgery for recurrent malignant gliomas.
Authors: Hall W A , Djalilian H R , Sperduto P W , Cho K H , Gerbi B J , Gibbons J P , Rohr M , Clark H B 
Published: February 2017

PURPOSE To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas. PATIENTS AND METHODS We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA). RESULTS The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury. CONCLUSION Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.
Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis.
Authors: Langer C J , Leighton J C , Comis R L , O'Dwyer P J , McAleer C A , Bonjo C A , Engstrom P F , Litwin S , Ozols R F 
Published: February 2017

PURPOSE To determine the activity and toxicity of combination paclitaxel (24 hours) and carboplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Eligibility required measurable disease (stage IV or stage IIIB with malignant pleural effusion), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count > or = 2,000/microL, platelet count > or = 100,000/microL serum creatinine concentration < or = 1.5 mg/dL, and bilirubin level < or = 2 mg/dL. Paclitaxel was initially administered at a dose of 135 mg/m2/d, followed by carboplatin on day 2 at a targeted area under the concentration-time curve (AUC) of 7.5 using the Calvert formula. Granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In patients who sustained less than grade 4 myelosuppression, the paclitaxel dose was sequentially escalated 40 mg/m2 per cycle to a maximum of 215 mg/m2. Treatment was repeated at 3-week intervals for six cycles. RESULTS From June 1993 through February 1994, 54 patients were enrolled; 53 are assessable for toxicity and response. The median age was 62 years (range, 34 to 84). Sixty-nine percent were male, 65% had adenocarcinoma, and 93% had stage IV disease. Two hundred sixty-eight cycles were administered; 32 patients (59%) completed all six cycles. Twenty-five unanticipated hospitalizations occurred during treatment (9.3% of cycles) in 20 patients (37%). Myelosuppression was the principal toxicity; grade 3 or 4 granulocytopenia occurred in 57% of patients after the first cycle, but decreased to 35% during the second cycle after introduction of G-CSF and consistently remained < or = 22% during subsequent cycles. Seven episodes of neutropenic fever occurred, all during the first cycle. Grade 3 or 4 thrombocytopenia and anemia occurred in 47% and 33% of patients, respectively. Eight patients (15%) required platelet transfusions and 16 (30%) required packed RBC support. Neuropathy, myalgias/arthralgias, and thrombocytopenia, although generally mild, were cumulative. The paclitaxel dose was boosted to 215 mg/m2 in > or = 70% of patients who received three or more cycles. At an AUC of 7.5, the median first-cycle carboplatin dose was 424 mg/m2 (range, 273 to 709 mg/m2). The objective response rate was 62%, with five (9%) complete responses and 28 (53%) partial responses. The median progression-free survival time was 28 weeks and the median survival time 53 weeks. The 1-year survival rate is 54%. CONCLUSION The paclitaxel-carboplatin combination is active in advanced NSCLC and may enhance survival; it merits further investigation in phase III trials.
Controlled trial of dexverapamil, a modulator of multidrug resistance, in lymphomas refractory to EPOCH chemotherapy.
Authors: Wilson W H , Bates S E , Fojo A , Bryant G , Zhan Z , Regis J , Wittes R E , Jaffe E S , Steinberg S M , Herdt J 
Published: February 2017

PURPOSE Overexpression of the multidrug resistance gene (mdr-1) is present in up to 60% of relapsed lymphomas. To study its role in lymphomas, we conducted a controlled trial of dexverapamil, an inhibitor of the mdr-1 gene product, P-glycoprotein (Pgp), in lymphomas refractory to etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. PATIENTS AND METHODS Eligible patients had recurrent Hodgkin's (HD) or non-Hodgkin's lymphomas (NHL) and measurable disease. Patients initially received EPOCH alone and those with stable tumor over two cycles or progressive disease crossed over to receive dexverapamil and EPOCH on subsequent cycles. Dexverapamil was escalated eight dose levels, from 240 to 1,200 mg/m2/d. When possible, serial biopsies were obtained to measure mdr-1 expression by quantitative polymerase chain reaction (PCR). RESULTS Of 154 patients entered onto the trial, 109 had NHL and 45 had HD. The median age was 44 years, 67% had stage IV disease, and the median number of prior regimens was two (range, one to 12) in NHL and one (range, one to four) in HD. Sixty-four patients (42%) crossed over, of which eight were not assessable. The maximum-tolerated dose of dexverapamil was 900 mg/m2/d. Among 41 NHL patients (excluding mycosis fungoides), there were three complete responses (CRs) and two partial responses (PRs) (12%) and five minor responses (MRs); two of 10 HD patients achieved PRs. The mdr-1 level was measured in 44 biopsies from 19 patients. Pretherapy, mdr-1 was low (median, 2.5 U) but increased (median, 12.2 U) at crossover. Of six patients with mdr-1 levels greater than 15 U, three responded to dexverapamil, while only one of eight patients with mdr-1 levels less than 15 U responded. EPOCH and dexverapamil were well tolerated, but compared with EPOCH alone, produced more hematologic toxicity. CONCLUSION These results suggest that Pgp plays a role in clinical drug resistance of lymphomas. However, they also suggest that mechanisms other than Pgp are prominent in heavily pretreated patients and that, although Pgp inhibition may be necessary, it is probably insufficient. Earlier intervention with dexverapamil may be more effective and warrants further study.
Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B.
Authors: Canellos G P , Petroni G R , Barcos M , Duggan D B , Peterson B A 
Published: February 2017

PURPOSE To evaluate the activity and toxicity of combined etoposide, vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). PATIENTS AND METHODS Eligible patients were more than 15 years of age and had received only one prior course of MOPP and were in relapse with measurable disease. The EVA regimen (etoposide 100 mg/m2 intravenously [IV] on days 1, 2, and 3; vinblastine 6 mg/m2 IV on day 1; and doxorubicin 50 mg/m2 IV on day 1) was administered every 28 days for a minimum of four and a maximum of six cycles. Patients were restaged at 3 and 6 months. RESULTS Forty-five eligible patients were treated, with an overall response rate of 73%. There were 40% complete responses (CRs) and 33% partial responses (PRs). The median follow-up time in 42 months. The median time to treatment failure (TTF) is 10 months, with 31% continuing progression-free. Eighteen patients achieved a second CR, with only seven recurrences in that group. Failure-free survival and overall survival were significantly better in patients whose first MOPP-induced remission was longer than 12 months and who were free of B symptoms at relapse. Toxicity was primarily myelosuppression, which resulted in two toxic deaths. Pulmonary toxicity was not observed. CONCLUSION EVA is an effective second-line regimen for the treatment of HD in relapse following MOPP chemotherapy.
Tandem autotransplantation for the treatment of metastatic breast cancer.
Authors: Broun E R , Sridhara R , Sledge G W , Loesch D , Kneebone P H , Hanna M , Hromas R , Cornetta K , Einhorn L H 
Published: February 2017

PURPOSE To investigate the tolerability and impact on progression-free and overall survival of two consecutive cycles of high-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) in patients with previously untreated metastatic breast cancer. PATIENTS AND METHODS Twenty-eight patients received conventional-dose induction therapy (ITx) followed by a planned two cycles of HDC with ABMT. Median age was 45 years (range, 34 to 60 years). Sites of disease were bone (seven patients), visceral (three), soft tissue (11), multiple (six), and CNS (one). The ITx regimens of cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, fluorouracil, prednisone, and tamoxifen (CAMFTP) (three patients); fluorouracil, doxorubicin, and cyclophosphamide (FAC; 11 patients); cyclophosphamide, methotrexate, and fluorouracil (CMF; four patients); or doxorubicin or mitoxantrone/cyclophosphamide (10 patients) were given to maximum response (three to five cycles). HDC was cyclophosphamide 6 g/m2, carboplatin 2 g/m2, and etoposide 625 mg/m2 with ABMT. RESULTS Of 28 patients, 24 received two (86%) cycles of HDC. Four received only one cycle due to persistent toxicity from course 1 (one patient), no response to course 1 (two), and death on course 1 (one). Grade 3 to 4 nonhematologic toxicities included mucositis (in one or both cycles in 21 of 28 patients; 75%), diarrhea, nausea, and vomiting. Reversible peripheral neuropathy was seen in 15 of 28 patients and was severe in one. Documented infections were seen in 19 of 52 cycles. There was one transplant-related death. Six patients were converted from partial remission (PR) to complete remission (CR) with HDC; two of 24 patients (8%) were converted from PR to CR with the second cycle of HDC. Progression-free survival rate is nine of 28 patients (32%) with median follow-up of 23 months (range, 13 to 36+ months). Eighteen of 28 patients (64%) have progressed at 1 to 17 months from ABMT. CONCLUSION Two cycles of HDC with ABMT was well tolerated with a high response rate in patients with metastatic breast cancer. The importance of the second cycle of HDC in this population is unclear.
Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.
Authors: Abrams J S , Vena D A , Baltz J , Adams J , Montello M , Christian M , Onetto N , Desmond-Hellmann S , Canetta R , Friedman M A 
Published: February 2017

PURPOSE To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. PATIENTS AND METHODS Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. RESULTS In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. CONCLUSION Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease.
Salvage chemotherapy with paclitaxel for recurrent primary brain tumors.
Authors: Chamberlain M C , Kormanik P 
Published: February 2017

PURPOSE To assess the safety and efficacy of Taxol (paclitaxel; Bristol-Myers Squibb Co, Princeton, NJ) given at a dose of 175 mg/m2 every 3 weeks as a 3- to 4-hour outpatient infusion to patients with recurrent malignant primary brain tumors who had received prior radiotherapy and at least one chemotherapy regimen containing nitrosoureas and who were no longer responding to therapy. PATIENTS AND METHODS Twenty patients (12 men and eight women), ages 19 to 69 years (median, 35), with recurrent primary brain tumors were treated according to a phase II protocol with intravenous Taxol. Tumor histologies included the following: anaplastic astrocytoma (n = 8), glioblastoma multiforme (n = 8), and anaplastic oligodendroglioma (n = 4). All patients had been previously treated with subtotal resection, limited-field radiotherapy (median dose, 60 Gy; range, 54 to 78 Gy), and nitrosourea-based chemotherapy. Taxol was administered intravenously at a dose of 175 mg/m2/d every 3 weeks with neurologic and neuroradiographic evaluation every 8 to 9 weeks. Complete blood cell counts were performed weekly. RESULTS A median of six cycles of Taxol (range, two to 12) were administered to 20 assessable patients. Toxicities included partial alopecia (n = 10), thrombocytopenia (n = 4), rate of Taxol administration-dependent bradycardia (n = 3), and nondisabling peripheral neuropathy (n = 1). No patient developed neutropenic fever or sepsis or required cytokine support. Two patients required blood-product support (platelet transfusions in both). Four patients (20%) demonstrated a partial response (PR) and seven (35%) had stable disease (SD) for a total response plus SD rate of 55%. The median time to tumor progression was 6 months (range, 2 to 20). CONCLUSION Taxol demonstrated modest efficacy with minimal toxicity in this heavily pretreated cohort of young patients with recurrent primary brain tumors.
Modulation of O6-alkylguanine alkyltransferase-directed DNA repair in metastatic colon cancers.
Authors: Willson J K , Haaga J R , Trey J E , Stellato T A , Gordon N H , Gerson S L 
Published: February 2017

PURPOSE Carmustine (BCNU) resistance has been correlated with tumor expression of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AT). It has been shown that streptozotocin will deplete AT activity of human colon cancer cells in vitro and potentiate BCNU cytotoxicity. This clinical trial was conducted to determine whether streptozotocin can be used as a modulator of AT in metastatic colorectal cancers and thereby overcome clinical resistance to BCNU. PATIENTS AND METHODS Fifteen patients with fluorouracil-resistant metastatic colon or rectal cancers were treated sequentially with 2 g/m2 of streptozotocin followed 5 1/2 hours later by BCNU. Sequential biopsies of metastases before and after streptozotocin were conducted to determine whether streptozotocin depletes tumor AT. Peripheral-blood mononuclear cells (PBMCs) were evaluated as a surrogate tissue for prediction of baseline AT levels and streptozotocin posttreatment modulation of the AT in metastases. RESULTS Streptozotocin treatment led to a 78% (range, 69% to 89%) decrease in the AT levels in colon cancer metastases; however, myelosuppression and hepatic toxicity limited the BCNU dose to 130 mg/m2. A similar decrease in AT levels of PBMCs was found; however, the absolute levels of AT in PBMCs at baseline and following streptozotocin were not predictive of the levels expressed in metastases from the same patient. Despite the decrease in tumor levels of AT, no clinical responses were observed. CONCLUSION Streptozotocin decreases but does not fully deplete AT activity in metastatic colorectal cancers and the residual AT level in metastases is sufficient to maintain clinical resistance to BCNU. We have also demonstrated that sequential computed tomography (CT)-directed biopsies of colorectal cancer metastases can be used to evaluate strategies to investigate modulators of AT-directed repair. AT levels of PBMCs do not predict for the AT level or degree of modulation achieved in the metastatic tumor.
Lymph node staging standards in gastric cancer.
Authors: Bunt A M , Hogendoorn P C , van de Velde C J , Bruijn J A , Hermans J 
Published: February 2017

PURPOSE In tumor-node-metastasis (TNM) staging, no recommendations are provided on the number of lymph nodes to examine per N level. We investigated the relationship between number of nodes examined and probability of detecting metastases, and ultimately staging accuracy. PATIENTS AND METHODS Data from 473 curatively resected gastric cancer patients, from a randomized trial that compared the Western resection with limited and the Japanese resection with extended lymphadenectomy, were used. RESULTS Yields varied between zero to 67 in N1 and zero to 43 in N2. Yields correlated significantly with classification; the more nodes examined, the more likely the classification was N+. Calculating the probability of detecting metastases using either a likelihood-ratio estimate or an exponential model, this probability increased steeply in the lower range and more gradually in the higher range yield. CONCLUSION To standardize treatment results, we emphasize histologic examination of a fixed number of nodes per anatomically defined N level (20 in N1 and 15 in N2), corresponding with a probability to detect metastases of 60% to 65% and 40% to 45%, respectively. These yields are feasible in all resection specimens, while the extra increase in the chance of detecting metastases by examining more nodes does not compensate the effort to increase yields further. Thus, standardization of histologic TNM staging can improve and render comparison of surgical and adjuvant treatment modalities feasible.
Bone marrow-sparing and prevention of alopecia by AS101 in non-small-cell lung cancer patients treated with carboplatin and etoposide.
Authors: Sredni B , Albeck M , Tichler T , Shani A , Shapira J , Bruderman I , Catane R , Kaufman B , Kalechman Y 
Published: February 2017

PURPOSE The aim of this study was to evaluate the ability of the immunomodulator AS101 to prevent chemotherapy-induced neutropenia and thrombocytopenia and thus allow patients to receive full-dose antineoplastic agents according to protocol design. We also aimed to determine the production level of various hematopoietic growth factors in treated patients. PATIENTS AND METHODS This study of 44 unresectable or metastatic non-small-cell lung cancer (NSCLC) patients was an open-label prospective randomized study of standard chemotherapy alone versus chemotherapy plus AS101. Each patient received carboplatin (300 mg/m2 intravenously [IV] on day 1 of a 28-day cycle, and etoposide (VP-16) (200 mg/m2 orally) on days 3, 5, and 7 of each cycle. AS101 was administered at 3 mg/m2 three times per week starting 2 weeks before chemotherapy. RESULTS AS101, which manifested no major toxicity, significantly reduced neutropenia and thrombocytopenia and thus allowed all treated patients to receive full-dose antineoplastic agents, in contrast to only 28.5% of the control group. Continuous treatment with AS101 significantly reduced the number of days per patient of thrombocytopenia and neutropenia and did not provide protection to tumor cells as reflected by the higher overall response rate compared with the chemotherapy-alone arm. Interestingly, AS101 treatment also significantly prevented chemotherapy-induced alopecia. These effects correlate with the ability of AS101-treated patients to increase significantly the production of colony-stimulating factors (CSFs) interleukin-1 alpha (IL-1 alpha) and IL-6. CONCLUSION AS101 has significant bone marrow (BM)-sparing effects and prevents hair loss in chemotherapy-treated patients, with minimal overall toxicity. These effects are probably due to increased production of IL-1 alpha, IL-6, and granulocyte-macrophage (GM)-CSF.
Ethical considerations in oncology: balancing the interests of patients, oncologists, and society.
Authors: Smith T J , Bodurtha J N 
Published: February 2017

BACKGROUND Oncologists face ethical dilemmas every day in deciding about choice of treatment, continuation of treatments, events near the end of life, conflicts of interest, and risk management. Yet, many oncologists have limited training in ethics. METHODS Review of existing studies and definitions of useful terms. Case studies analyzed according to ethical principles. RESULTS Individual oncology cases can be analyzed according to ethical principles with benefit to the patient, physician, and possibly society. Ethics cannot resolve many of the thorny questions about allocation of resources, justice, or possible conflict of interest. CONCLUSION Oncology decision-making fits into formal ethical frameworks, and understanding both can help doctors and patients make difficult choices. Understanding of ethical principles can help daily practice, but does not solve current dilemmas of allocation of resources, unrealistic demands, etc. More formal collaboration between hospital ethics committees or personnel and clinical oncologists is recommended for the day-to-day decision-making process.