bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast conservation and prolonged chemotherapy for locally advanced breast cancer: the University of Michigan experience.
Authors: Merajver S D , Weber B L , Cody R , Zhang D , Strawderman M , Calzone K A , LeClaire V , Levin A , Irani J , Halvie M , August D , Wicha M , Lichter A , Pierce L J 
Published: February 2017

PURPOSE To determine whether breast conservation and prolonged neoadjuvant chemotherapy have efficacy in locally advanced breast cancer (LABC), as measured by survival and rate of breast conservation. MATERIALS AND METHODS Eighty-nine patients with stage III disease were enrolled at the University of Michigan (UM) onto a prospective nonrandomized trial. Patients received nine 21-day cycles of neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and cyclophosphamide 750 mg/m2 intravenously on day 1, conjugated estrogens 0.625 mg orally twice daily on days 6 to 8, methotrexate 40 mg/m2 and fluorouracil 500 mg/m2 intravenously on day 8, and tamoxifen 10 mg orally twice daily on days 9 to 14. Patients with a negative biopsy received radiation only, while those with residual disease underwent mastectomy and postoperative radiotherapy. Eight more cycles of chemohormonal therapy were administered after local-regional therapy. RESULTS The clinical response rate to neoadjuvant therapy was 97%, 28% of patients had a complete pathologic response evaluated at biopsy. Five-year overall and disease-free survival probabilities were 54% and 44%, respectively. The median disease-free survival time was 2.4 years. The 5-year actuarial rates of local-regional control with local failure as only first failure were 82% and 78% following radiotherapy, and mastectomy and radiotherapy, respectively (P = .99). CONCLUSION Prolonged neoadjuvant chemohormonal therapy and biopsy-driven local therapy have efficacy in LABC, with 28% of patients being candidates for breast conservation and a 5-year overall survival rate of 54%.
Phase II trial of irinotecan in patients with metastatic colorectal carcinoma.
Authors: Pitot H C , Wender D B , O'Connell M J , Schroeder G , Goldberg R M , Rubin J , Mailliard J A , Knost J A , Ghosh C , Kirschling R J , Levitt R , Windschitl H E 
Published: February 2017

PURPOSE To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT-11). PATIENTS AND METHODS A total of 121 patients with advanced colorectal carcinoma--90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients--were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. RESULTS Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy-naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11.9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with > or = grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (chi2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. CONCLUSION According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.
Combined modality therapy for stage II and stage III pancreatic carcinoma.
Authors: Kamthan A G , Morris J C , Dalton J , Mandeli J P , Chesser M R , Leben D , Cooperman A , Bruckner H W 
Published: February 2017

PURPOSE To study the outcome achieved with three-drug chemotherapy and split-course external-beam radiotherapy as a treatment for unresectable stage II and III pancreatic carcinoma. PATIENTS AND METHODS Radiotherapy was given in three cycles of 2 Gy/d on days 1 to 5 and 8 to 12 (total dose, 54 Gy) concurrently with fluorouracil (FU) 1,000 mg/m2/d by continuous infusion for 4.5 days, streptozocin (STZ) 300 mg/m2 on days 1, 2, and 3 and cisplatin (P) 100 mg/m2 on day 3 of each every-28-day cycle. Subsequent treatment consisted of leucovorin (LV) 200 mg/m2 and FU 600 to 1,000 mg/m2 every 14 days. RESULTS The median survival time for the 35 patients was 15 months and 26% of patients were alive at 24 months. Fifteen patients (42.8%) had objective responses to therapy. Six (17%) had a complete response (CR). Three of nine patients with partial responses (PRs) achieved a radiographic CR within the next 3 months. Nine patients underwent attempts at surgical resection: five were resected (median survival time, 31 months; range, 12.8 to 44.7+), two had no residual disease found at complete resection, and three others also had a complete resection. Of four others who could not be resected, three underwent intraoperative radiotherapy and one had occult metastatic disease. Of primary tumors, 91% did not produce either back pain or local gastrointestinal complications for 2 years. The rates of severe side effects were stomatitis 15%, anemia 14%, granulocytopenia 6%, and thrombocytopenia 6%. CONCLUSION Palliation and survival compare favorably with other series, including many surgical series. The response findings encourage studies of both unresectable and (as neoadjuvant therapy) resectable tumors.
Cost of combined modality interventions for stage III non-small-cell lung cancer.
Authors: Evans W K , Will B P , Berthelot J M , Earle C C 
Published: February 2017

PURPOSE To evaluate the cost-effectiveness (CE) of new combined modality strategies in patients with stage III non-small-cell lung cancer (NSCLC). METHODS Recent studies suggest that combined modality therapy confers a survival advantage for patients with stage III NSCLC. Using the Statistics Canada (Ottawa, Canada) lung cancer costing model, we have evaluated the CE of these interventions using 1993 Canadian health care costs and the perspective of the government as payer in a universal health care system. RESULTS We estimate that the cost to treat a stage IIIa NSCLC patient with preoperative and postoperative chemotherapy would increase by $15,886, and a similar combined modality approach with the addition of postoperative radiotherapy would increase the cost by $22,963. Chemoradiotherapy for stage IIIb NSCLC would produce a smaller incremental cost of approximately $8,912 per case. However, these approaches are remarkably cost-effective, with cost per life-year gained (LYG) ranging from $3,348 to $14,958. Administering all chemotherapy in the outpatient department would improve CE. For sensitivity analysis, we reduced the survival gain that resulted from the three interventions by 25% and 50%, and increased the hospital per diem rates by 10%, 20%, and 30%. CONCLUSION Even with the most adverse assumptions, the CE estimates were all considered acceptable for new health care technologies in Canada. Overall, it appears that neoadjuvant therapy for stage IIIa NSCLC and combined modality therapy for stage IIIb NSCLC are cost-effective. Economic considerations should not be a barrier to their adoption.
Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer.
Authors: Piccart M J , Klijn J , Paridaens R , Nooij M , Mauriac L , Coleman R , Bontenbal M , Awada A , Selleslags J , Van Vreckem A , Van Glabbeke M 
Published: February 2017

PURPOSE To confirm the efficacy of docetaxel in patients with breast cancer previously treated with one chemotherapy regimen for advanced or metastatic disease and to compare the incidence of fluid retention (FR) and skin toxicity when docetaxel is administered with and without prophylactic corticosteroids. PATIENTS AND METHODS Eighty-three patients, pretreated with one chemotherapy regimen for metastatic breast cancer (MBC) with bidimensionally measurable and progressive disease, were eligible for this randomized trial. Docetaxel with prophylactic oral antihistamine was administered at a dose of 50 mg/m2 as a 1-hour infusion on days 1 and 8 every 21 days and patients were randomized to receive methylprednisolone (40 mg days -1, 0, 1, 7, 8, and 9 of each cycle) (arm A) or no methylprednisolone (arm B). RESULTS Twenty-eight patients (34%, 95% confidence interval [CI], 23% to 45%) achieved on objective response. The median time to disease progression and median overall survival time were 5 and 13.5 months, respectively. In total, 415 cycles of docetaxel were administered (arm A: N = 219, median = six; arm B: N = 196, median = five). The most common toxicity observed was grade 3 or 4 neutropenia, which occurred in 79% of patients. Clinically significant nonhematologic side effects included skin reactions and asthenia. In an intent-to-treat analysis, patients who received methylprednisolone premedication had a delayed onset of FR (median time to onset of FR: arm A, 84 days; arm B, 62 days; P = .01) and received a higher median cumulative dose of docetaxel before the onset of FR (arm A, 333 mg/m2; arm B, 215 mg/m2; P = .001). There was no statistically significant difference in the incidence of skin toxicity between the two arms. CONCLUSION Docetaxel, at this dose and schedule, has definite antitumor activity in pretreated MBC patients. Moreover, this is the first randomized trial to show that corticosteroids have a favorable impact on docetaxel-induced FR.
Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation.
Authors: Hesdorffer C , Ayello J , Ward M , Kaubisch A , Vahdat L , Balmaceda C , Garrett T , Fetell M , Reiss R , Bank A , Antman K 
Published: February 2017

PURPOSE Normal bone marrow cells have little or no expression of the MDR p-glycoprotein product and, therefore, are particularly susceptible to killing by MDR-sensitive drugs, such as vinca alkaloids, anthracyclines, podophyllins, and paclitaxel and its congeners. Here we report the results of a phase I clinical trial that tested the safety and efficacy of transfer of the human multiple drug resistance (MDR1, MDR) gene into hematopoietic stem cells and progenitors in bone marrow as a means of providing resistance of these cells to the toxic effects of cancer chemotherapy. PATIENTS AND METHODS Up to one third of the harvested cells of patients who were undergoing autologous bone marrow transplantation as part of a high-dose chemotherapy treatment for advanced cancer were transduced with an MDR cDNA-containing retrovirus; these transduced cells were reinfused together with unmanipulated cells after chemotherapy. RESULTS High-level MDR transduction of erythroid burst-forming unit (BFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM) derived from transduced CD34+ cells was shown posttransduction and prereinfusion. However, only two of the five patients showed evidence of MDR transduction of their marrow at a low level at 10 weeks and 3 weeks, respectively, posttransplantation. The cytokine-stimulated transduced cells may be out-competed in repopulation by unmanipulated normal cells that are reinfused concomitantly. The MDR retroviral supernatant that was used was shown to be free of replication-competent retrovirus (RCR) before use, and all tests of patients' samples posttransplantation were negative for RCR. In addition, no adverse events with respect to marrow engraftment or other problems related to marrow transplantation were encountered. CONCLUSION These results indicate the feasibility and safety of bone marrow gene therapy with a potentially therapeutic gene, the MDR gene.
Preclinical and clinical studies of bone marrow uptake of fluorine-1-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy.
Authors: Sugawara Y , Fisher S J , Zasadny K R , Kison P V , Baker L H , Wahl R L 
Published: February 2017

PURPOSE To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on bone marrow glucose metabolism in rodents and in patients, as assessed by 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) uptake measured directly or by positron-emission tomography (PET) scanning. MATERIALS AND METHODS Groups of three rats received either daily saline, G-CSF, or GM-CSF injections for 7 days. After treatment, FDG was injected and F-18 activities in tissues measured 1 hour later. Twenty-two breast cancer patients treated with multiagent chemotherapy were sequentially studied with PET. Eleven patients received G-CSF therapy as an adjunct to chemotherapy, while 11 received chemotherapy only. The standardized uptake value-lean (SUL) of bone marrow FDG uptake was measured and compared. RESULTS In rats, bone marrow F-18 activity was significantly higher in both CSF groups than in the saline group (G-CSF, 0.44 +/- 0.08; GM-CSF, 0.33 +/- 0.02; saline, 0.18 +/- 0.02% injected dose [ID]/g x kg; P < .05), but the other normal tissues had comparable biodistributions to controls. In breast cancer patients, the FDG uptake of bone marrow did not change with chemotherapy alone; however, marrow uptake was increased after treatment with G-CSF. The dose of G-CSF and duration of treatment were correlated with the extent of increase in FDG uptake. The SUL of bone marrow was as follows: baseline, 1.56 +/- 0.23; after one cycle, 3.13 +/- 1.40 (P < .01); after two cycles, 2.22 +/- 0.85 (P < .05); and after three cycles, 2.14 +/- 0.79 (P < .05), respectively. Although the FDG uptake of bone marrow declined after G-CSF treatment was completed, it was higher than the baseline level for up to 4 weeks postcompletion of G-CSF and the elevated marrow FDG uptake was sustained longer than the period of blood neutrophil count elevation. CONCLUSION Substantial increases in bone marrow FDG uptake are rapidly induced by CSF treatments and should not be misinterpreted as diffuse bone marrow metastases.
Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study.
Authors: Talcott J A , Rieker P , Clark J A , Propert K J , Weeks J C , Beard C J , Wishnow K I , Kaplan I , Loughlin K R , Richie J P , Kantoff P W 
Published: February 2017

PURPOSE To assess complications of therapy for early (nonmetastatic) prostate cancer. PATIENTS AND METHODS A prospective study of a cohort of 279 men who sought treatment advice and completed required pretreatment forms. The measures were self-reported patient symptoms and other measures of quality of life before therapy and at 3 and 12 months afterward. RESULTS Bowel and bladder symptoms were uncommon pretreatment. Patients frequently reported irritative bowel and bladder symptoms at 3 months after radiotherapy, although these subsided somewhat at 12 months. Substantial ("a lot") urinary incontinence and wearing of absorptive pads were reported by 11% and 35% at 12 months after surgery and varied little by age. Incontinence occurred after radiotherapy infrequently, and only in men more than 65 years old. Inadequate erections, present in one third of men pretreatment, were nearly universal at 3 months after surgery, although some improvement, primarily in men under 65 years of age, was evident at 12 months. Sexual dysfunction after radiotherapy increased less but continually through 12 months, suggesting that observed treatment-related differences would decline with further follow-up. CONCLUSION External-beam radiotherapy of early prostate cancer is followed by bowel and bladder irritability, by increasingly severe sexual dysfunction and, in men aged more than 65 years, occasional urinary incontinence. Greater sexual dysfunction and urinary incontinence occur in the year following radical prostatectomy. These postsurgical complication rates from patient questionnaires are greater than have been reported in other treatment series and confirm the results of two retrospective studies of patient-reported complications.
Tamoxifen and toremifene in breast cancer: comparison of safety and efficacy.
Authors: Buzdar A U , Hortobagyi G N 
Published: February 2017

PURPOSE Tamoxifen is currently the standard hormonal treatment of breast cancer, both for metastatic disease and in the adjuvant setting. A new antiestrogen, toremifene, was approved recently for use in managing metastatic breast cancer in postmenopausal women. METHODS Toremifene is structurally similar to tamoxifen, differing only by a single chlorine atom, and has a similar pharmacologic profile. The major difference between the two compounds is in the preclinical activity; chronic, high-dose tamoxifen is hepatocarcinogenic in the rat, whereas toremifene is not. Neither agent is hepatocarcinogenic in mice, hamsters, or humans; therefore, clinical relevance of the rat data may not be significant. RESULTS In a worldwide phase III trial, the two agents demonstrated comparable efficacy and safety against metastatic breast cancer. Both agents have shown a significant hypocholesterolemic effect after long-term administration. CONCLUSION Due to the paucity of long-term clinical data on toremifene, important unresolved questions remain, which include its effects on bone mineral density, the frequency of cardiac events, and the risk for endometrial cancer. Tamoxifen has been associated with maintenance of bone mineral density, a reduction in cardiac events, and a slightly increased risk of endometrial cancer. Toremifene is not likely to be used as second-line therapy after tamoxifen failure due to cross-resistance, and its ultimate place in therapy of advanced breast cancer remains to be determined.
Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.
Authors: Hagenbeek A , Carde P , Meerwaldt J H , Somers R , Thomas J , De Bock R , Raemaekers J M , van Hoof A , De Wolf-Peeters C , van Glabbeke M 
Published: February 2017

PURPOSE Interferon alfa has shown significant activity in patients with low-grade malignant non-Hodgkin's lymphoma (NHL). In 1985, we initiated a prospective randomized study in which the potential benefit of interferon alfa given as maintenance treatment was investigated after tumor load reduction was achieved with chemoradiotherapy in patients with advanced low-grade malignant non-Hodgkin's lymphoma. PATIENTS AND METHODS The study involved 347 patients with stage III or IV disease, 315 satisfying the eligibility criteria. All were treated with a regimen of cyclophosphamide, vincristine, and prednisone (CVP) given every 3 weeks for eight cycles. Thereafter, patients were eligible for iceberg irradiation. Finally, all patients were completely restaged, and responding and stable-disease patients were then randomized, 122 to interferon alfa-2a maintenance, 3 million U three times weekly for 1 year; and 120 to no further treatment. RESULTS Seventy-nine percent of the patients response to CVP, ie, 45% complete remissions (CR) and 34% partial remissions (PR). In the group of randomized patients, the response rate after CVP plus or minus radiotherapy was 90%. As compared with control patients, patients in the interferon (IFN) maintenance group had a tendency toward a prolonged time to progression (TTP) (median, 132 v 87 weeks; P = .054, adjusted for response to CVP). However, overall survival was similar in both groups. Interferon was well tolerated. The median dose of IFN actually received corresponded to 90% of the planned cumulative dose. The treatment had to be stopped because of toxicity in 16 patients (15% of the patients in whom IFN was started). CONCLUSION Interferon maintenance treatment in the phase of minimal residual disease of patients with advanced low-grade malignant NHL increased TTP at the borderline of statistical significance, without remarkable toxicity. However, overall survival was not influenced.
Tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer: a phase II study.
Authors: Treat J , Johnson E , Langer C , Belani C , Haynes B , Greenberg R , Rodriquez R , Drobins P , Miller W , Meehan L , McKeon A , Devin J , von Roemeling R , Viallet J 
Published: February 2017

PURPOSE A phase II study was conducted to evaluate the safety and efficacy of tirapazamine combined with cisplatin for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-four patients with stage IIIB/IV NSCLC were treated with a combination of tirapazamine and cisplatin. Patients received tirapazamine 260 mg/m2 administered intravenously over 2 hours, followed 1 hour later by cisplatin 75 mg/m2 administered over an additional hour, repeated every 21 days. The duration of therapy was meant to be limited to four cycles for nonresponders and eight cycles for responders. RESULTS Ten of 44 patients (23%) showed a partial response. The estimated median survival for all patients was 37 weeks. Toxicities were treatable and included grade 3 nausea or vomiting (25%), fatigue (27.3%), and muscle cramps (4.5%). No dose reductions were necessary. CONCLUSION The results show that tirapazamine can safely be added to cisplatin. Both the median survival and response rate observed strongly suggest that tirapazamine with cisplatin is more active than cisplatin alone.
Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital.
Authors: Walter A W , Hancock M L , Pui C H , Hudson M M , Ochs J S , Rivera G K , Pratt C B , Boyett J M , Kun L E 
Published: February 2017

PURPOSE To evaluate the incidence of and potential risk factors for second malignant neoplasms of the brain following treatment for childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS The study population consisted of 1,612 consecutively enrolled protocol patients treated on sequential institutional protocols for newly diagnosed ALL at St Jude Children's Research Hospital (SJCRH) between 1967 and 1988. The median follow-up duration is 15.9 years (range, 5.5 to 29.9 y). RESULTS The cumulative incidence of brain tumors at 20 years is 1.39% (95% confidence interval [CI], 0.63% to 2.15%). Twenty-two brain tumors (10 high-grade gliomas, one low-grade glioma, and 11 meningiomas) were diagnosed among 21 patients after a median latency of 12.6 years (high-grade gliomas, 9.1 years; meningiomas, 19 years). Tumor type was linked to outcome, with patients who developed high-grade tumors doing poorly and those who developed low-grade tumors doing well. Risk factors for developing any secondary brain tumor included the presence of CNS leukemia at diagnosis, treatment on Total X therapy, and the use of cranial irradiation, which was dose-dependent. Age less than 6 years was associated with an increased risk of developing a high-grade glioma. CONCLUSION This single-institution study, with a high rate of long-term data capture, demonstrated that brain tumors are a rare, late complication of therapy for ALL. We report many more low-grade tumors than others probably because of exhaustive long-term follow-up evaluation. The importance of limiting cranial radiation is underscored by the dose-dependent tumorigenic effect of radiation therapy seen in this study.