bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Hematopoietic Growth Factor PIXY321 After Moderate-Dose Fluorouracil, Doxorubicin, and Cyclophosphamide in Stage II and III Breast Cancer
Authors: Jones Stephen E. , Khandelwal Pankaj , McIntyre Kristi , Mennel Robert , Orr Douglas , Kirby Robert , Agura Edward , Duncan Lewis , Hyman William , Roque Tammy , Regan David , Schuster Michael , Dimitrov Nikolay , Garrison Leslie , Lange Mary 
Published: February 2017

PURPOSE: To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m2, doxorubicin 60 mg/m2, and cyclophosphamide 750 mg/m2 (FAC) chemotherapy in patients with stage II and III breast cancer. PATIENTS AND METHODS: In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 μg/m2 subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/μL. RESULTS: PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P < .05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug. CONCLUSION: PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.
Biologic Markers as Predictors of Clinical Outcome From Systemic Therapy for Primary Operable Breast Cancer
Authors: Chang J. , Powles T. J. , Allred D. C. , Ashley S. E. , Clark G. M. , Makris A. , Assersohn L. , Gregory R. K. , Osborne C. K. , Dowsett M. 
Published: February 2017

PURPOSE: To determine whether pretreatment clinical features and molecular markers, together with changes in these factors, can predict treatment response and survival in patients with primary operable breast cancer who receive neoadjuvant therapy. PATIENTS AND METHODS: Mitoxantrone, methotrexate (with or without mitomycin), and tamoxifen chemoendocrine therapy was administered to 158 patients before surgery. Clinical response was assessed after four cycles of treatment. Fine-needle aspiration cytology for estrogen receptor (ER), progesterone receptor (PgR), c-erbB-2, p53, bcl-2, Ki67, S-phase fraction (SPF), and ploidy were performed pretreatment and repeated on day 10 or day 21 after the first cycle of treatment. RESULTS: Good clinical response (GCR, defined as complete response or minimal residual disease) was achieved in 31% of patients (49 of 158). Tumor size, nodal disease, response, ER, PgR, c-erbB-2, p53, bcl-2, Ki67, SPF, and ploidy were analyzed as predictors of survival. By univariate analysis, node-positive disease (P = .05), lack of ER (P < .05) and PgR (P < .05), and failure to attain GCR (P = .008) were associated with a significantly increased risk of relapse. A significantly increased risk of death was associated with node-positive disease (P = .02), lack of ER expression (P = .04), and failure to attain GCR. By multivariate analysis, GCR was an independent predictor for survival (P = .05). ER expression (P = .03), absence of c-erbB-2 (P = .03), and a decrease in Ki67 on day 10 or day 21 of the first cycle (P < .05) significantly predicted for subsequent GCR. CONCLUSION: Molecular markers may be used to predict the likelihood of achieving GCR, which seems to be a valid surrogate marker for survival.
Randomized Trial of a Slow-Release Versus a Standard Formulation of Cytarabine for the Intrathecal Treatment of Lymphomatous Meningitis
Authors: Glantz Michael J. , LaFollette Suzanne , Jaeckle Kurt A. , Shapiro William , Swinnen Lode , Rozental Jack R. , Phuphanich Surasak , Rogers Lisa R. , Gutheil John C. , Batchelor Tracy , Lyter David , Chamberlain Marc , Maria Bernard L. , Schiffer Charles , Bashir Rifaat , Thomas David , Cowens Wayne , Howell Stephen B. 
Published: February 2017

PURPOSE: To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chiron Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara-C) in the CSF of most patients for more than 14 days. PATIENTS AND METHODS: Twenty-eight patients with lymphoma and a positive CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month. Patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 2-week cycle. RESULTS: The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P = .006). All of the patients on the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trended in favor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P > .05). DepoCyt treatment was associated with an improved mean change in Karnofsky performance score at the end of induction (P = .041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease. CONCLUSION: DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.
Results of a European Organization for Research and Treatment of Cancer/Early Clinical Studies Group Phase II Trial of First-Line Irinotecan in Patients With Advanced or Recurrent Squamous Cell Carcinoma of the Cervix
Authors: Lhommé Catherine , Fumoleau Pierre , Fargeot Pierre , Krakowski Yvan , Dieras Véronique , Chauvergne Jacques , Vennin Philippe , Rebattu Paul , Roche Henry , Misset Jean-Louis , Lentz Marie-Ange , Van Glabbeke Martine , Matthieu-Boué Anne , Mignard Dominique , Chevallier Bernard 
Published: February 2017

PURPOSE: To determine the efficacy and tolerability of irinotecan (CPT-11) in advanced or recurrent cervical carcinoma. PATIENTS AND METHODS: Eligible patients had histologically confirmed, inoperable, progressive, metastatic or recurrent squamous cell cervical carcinoma and had received no radiotherapy in the preceding 3 months and had never received chemotherapy. The initial irinotecan dosage of 350 mg/m2 every 3 weeks was modifiable according to toxicity. Treatment continued for six cycles after complete response, or until disease progression or excessive toxicity after partial response, or for three additional cycles in the case of stable disease. Patients were stratified into group A (≥ one measurable lesion in a previously unirradiated area, with or without progressive disease in irradiated fields) or group B (measurable new lesion[s] in an irradiated field). RESULTS: Fifty-one of 55 enrolled patients were eligible for inclusion (median age, 47 years; range, 30 to 71 years). The response rate was 15.7% (95% confidence interval [CI], 7.0% to 28.6%) overall, 23.5% (95% CI, 10.7% to 41.2%) for group A (complete response, 2.9%), and zero for group B. The median time to progression and median survival were 4.0 and 8.2 months for group A and 2.5 and 4.2 months for group B, respectively. The major grade 3/4 toxicities for groups A and B were diarrhea (24.3% and 55.5%, respectively) and neutropenia (24.3% and 33.3%, respectively). There were four toxicity-related deaths, three in group B. Patients with no prior external pelvic irradiation experienced fewer grade 3 and 4 adverse events. CONCLUSION: Irinotecan is effective in treating cervical squamous cell carcinoma if disease is located in an unirradiated area. Because of toxicity, a reduced dose is advised for patients previously treated with external pelvic irradiation.
Predicting Cancer Progression in Patients With Stage T1 Bladder Carcinoma
Authors: Cheng Liang , Neumann Roxann M. , Weaver Amy L. , Spotts Bruce E. , Bostwick David G. 
Published: February 2017

PURPOSE: A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS: The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS: The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P = .037). The 5-year progression-free survival rate for patients with depth of invasion of ≥ 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P = .009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION: The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.
Mitomycin, Ifosfamide, and Cisplatin in Unresectable Non–Small-Cell Lung Cancer: Effects on Survival and Quality of Life
Authors: Cullen M. H. , Billingham L. J. , Woodroffe C. M. , Chetiyawardana A. D. , Gower N. H. , Joshi R. , Ferry D. R. , Rudd R. M. , Spiro S. G. , Cook J. E. , Trask C. , Bessell E. , Connolly C. K. , Tobias J. , Souhami R. L. 
Published: February 2017

PURPOSE: Chemotherapy for non–small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease. PATIENTS AND METHODS: Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses. RESULTS: Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P = .14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4.8 months (PC alone) (P = .03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P = .01) and after adjusting for prognostic factors (P = .01). CONCLUSION: MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.
Phase I/II Study of Vinorelbine, Mitomycin, and Cisplatin for Stage IIIB or IV Non–Small-Cell Lung Cancer
Authors: Furuse Kiyoyuki , Kawahara Masaaki , Nishiwaki Yutaka , Fukuoka Masahiro , Takada Minoru , Miyashita Mitsunori , Ohashi Yasuo 
Published: February 2017

PURPOSE: To determine the maximum-tolerated doses (MTDs) of vinorelbine (VRB), mitomycin (MMC), and cisplatin (P), given in two courses every 28 days to previously untreated patients with stage IIIB or IV non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: At least three or four patients were entered at each dose level. The starting dose was 20 mg/m2 for VRB on days 1 and 8 and 4 mg/m2 for MMC on day 1, with a fixed dose of P 80 mg/m2 on day 1 every 4 weeks. MMC was increased to 6 mg/m2 at dose level 2 and subsequently to 8 mg/m2 at dose level 4. At dose level 3, VRB was increased to 25 mg/m2. Twenty-five patients were entered onto the phase I study and 19 patients were entered onto phase II study. RESULTS: Nadir leukocyte and platelet counts decreased at each dose level. At dose levels 1 and 2, the dose-limiting toxicity (DLT) was not seen, but at dose levels 3 and 4, DLT was encountered in two patients. Nearly half the patients at dose level 4 had dose reduction due to grade 4 leukopenia. A mathematic model of all toxicity suggested that dose level 4 (VRB 25 mg/m2 on days 1 and 8 and MMC 8 mg/m2 and P 80 mg/m2 on day 1, every 4 weeks) would be the recommended dose for phase II study at which grade 4 toxicity is expected in ≤ 25% of patients over two courses. Of the 25 assessable patients in the phase I study, 13 achieved a partial response and one had a complete response for a response rate of 56.0%. Of the 19 assessable patients in the phase II study, 12 had a partial response (63.2%; 95% confidence interval, 38.4% to 83.7%). Grade 3 and 4 leukopenia was observed in 19 (100%), and grade 3 thrombocytopenia was seen in seven (36.8%). Median survival time was 10.7 months and the 1-year survival rate was 43.2% in the 44 assessable patients. CONCLUSION: The VRB/MMC/P regimen is effective against NSCLC, and its efficacy should be confirmed through a randomized study.
Cancer and Cardiac Mortality Among 15-Year Survivors of Cancer Diagnosed During Childhood or Adolescence
Authors: Green Daniel M. , Hyland Andrew , Chung Catherine S. , Zevon Michael A. , Hall Brenda C. 
Published: February 2017

PURPOSE: To evaluate the impact of cardiac disease and second malignant neoplasms on late mortality rate and to identify risk factors for late mortality among 15-year survivors of cancer diagnosed during childhood or adolescence. PATIENTS AND METHODS: Gender-specific all-cause and cause-specific (cardiac disease, cancer) standardized mortality ratios were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to survival. RESULTS: Patients who survived for 15 years after diagnosis had excess subsequent all-cause, cancer (second malignant neoplasms only), and cardiac mortality rates. No decrease in the late mortality rate by treatment era (1960 to 1970, 1971 to 1984) was identified. Risk factors for males included disease recurrence during the first 15 years after diagnosis, treatment with doxorubicin, and the diagnosis of Hodgkin's disease. Those for females included treatment with radiation therapy, treatment with an alkylating agent, and disease recurrence during the first 15 years after diagnosis. Cox regression analysis demonstrated that only an initial duration of remission of less than 15 years (P < .01) and treatment with doxorubicin (P = .08) were significantly associated with shorter survival time for males. No variable was significantly associated with shorter survival time for females in Cox regression analysis. CONCLUSION: Fifteen-year survivors of childhood cancer have excess mortality. More effective treatments must be developed to reduce this excess risk. Fifteen-year relapse-free survivors did not have excess mortality. This group will require continued observation to determine whether excess mortality will become apparent as more events occur.
Oral Etoposide for Refractory and Relapsed Neuroblastoma
Authors: Kushner Brian H. , Kramer Kim , Cheung Nai-Kong V. 
Published: February 2017

PURPOSE: To describe the efficacy of oral etoposide against resistant stage 4 neuroblastoma. PATIENTS AND METHODS: Patients with refractory or recurrent stage 4 neuroblastoma were treated with etoposide 50 mg/m2 taken orally each day, in two or three divided doses, for 21 consecutive days. Treatment could be repeated after a 1-week period. Extent-of-disease studies included imaging with 131-iodine-metaiodobenzylguanidine and extensive bone marrow (BM) sampling. RESULTS: Oral etoposide was used in 20 children between the ages of 2 and 11 years (median, 6 years). Prior treatment included high doses of alkylating agents and a median of 4.5 cycles of etoposide-containing chemotherapy, with cumulative etoposide doses of 1,800 mg/m2 to 3,935 mg/m2 (median, 2,300 mg/m2). Oral etoposide produced antineuroblastoma effects in four of four children with disease refractory to intensive induction treatment; sampling variability could account for resolution (n = 3) or reduction (n = 1) of BM involvement, but improvement in other markers also occurred. Antineuroblastoma effects were also evident in five of five children with asymptomatic relapses after a long chemotherapy-free interval: BM disease resolved and all other disease markers significantly improved in two patients, and disease markers improved or stabilized in three patients on treatment for more than 6 months. In these nine patients, extramedullary toxicity was absent, neutropenia did not occur, transfusional support was not needed, and preliminary data suggested little immunosuppression (phytohemagglutinin responses). Oral etoposide was ineffective in all (11 of 11) patients with rapidly growing tumor masses. CONCLUSION: Given the absence of toxicity to major organs, the minimal myelosuppression or immunosuppression, and the antineoplastic activity in patients with low tumor burdens after high-dose chemotherapy, limited use of low-dose oral etoposide should be considered for inclusion in postinduction consolidative treatment programs aimed at eradicating minimal residual disease.
Long-Term Outcomes After Function-Sparing Surgery Without Radiotherapy for Soft Tissue Sarcoma of the Extremities and Trunk
Authors: Baldini Elizabeth H. , Goldberg Joel , Jenner Christopher , Manola Judith B. , Demetri George D. , Fletcher Christopher D.M. , Singer Samuel 
Published: February 2017

PURPOSE: To define the rate of local recurrence (LR) and identify prognostic factors for LR for patients with soft tissue sarcoma (STS) treated with function-sparing surgery (FSS) without radiotherapy (RT). PATIENTS AND METHODS: Between 1970 and 1994, 242 patients with STS of the trunk and extremity presented with primary localized disease, 74 of whom were treated with FSS without RT (31%). The median tumor size was 4 cm (range, 0.5 to 31 cm). There were 40 patients with grade 1 tumors and 34 with grade 2 and 3 tumors. Median follow-up was 126 months. RESULTS: The 10-year actuarial local control rate was 93% ± 4%. Resection margin status was a significant predictor for LR. Patients with closest histologic resection margins of less than 1 cm had a 10-year local control rate of 87% ± 6% compared with 100% for patients with closest histologic resection margins of ≥ 1 cm (P = .04). There was no significant association between LR and tumor grade, size, site (truncal v extremity), or depth (superficial v deep). For all patients, the 10-year actuarial survival rate was 73% ± 6%. CONCLUSION: The 7% LR rate after treatment of STS with FSS without RT reported herein is comparable to published rates following treatment where adjuvant RT is used. These results suggest there may be a select subset of patients with STS in whom carefully performed FSS may serve as definitive therapy and in whom adjuvant RT may not be necessary. However, further study is needed to carefully define this subset of patients and to identify the optimal surgical approach and technique for patients treated without RT.
Neoadjuvant Chemotherapy With Doxorubicin and Cisplatin in Malignant Fibrous Histiocytoma of Bone: A European Osteosarcoma Intergroup Study
Authors: Bramwell Vivien H.C. , Steward William P. , Nooij Marianne , Whelan Jeremy , Craft Alan W. , Grimer Robert J. , Taminau Antonie H.M. , Cannon Steven R. , Malcolm Archie J. , Hogendoorn Pancras C.W. , Uscinska Barbara , Kirkpatrick Anne L. , Machin David , Van Glabbeke Martine M. 
Published: February 2017

PURPOSE: Studies involving small case series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival. In this study, we evaluated clinical and pathologic response rates and survival in a series of patients treated with a consistent chemotherapy regimen of doxorubicin and cisplatin (DOX/DDP). PATIENTS AND METHODS: Study patients were required to have biopsy-proven MFH-B, no previous chemotherapy, and primary or metastatic measurable disease and to be ≤ 65 years of age. Treatment consisted of doxorubicin 25 mg/m2/d days 1 through 3 and cisplatin 100 mg/m2 by 4-hour intravenous infusion every 3 weeks for six cycles. In patients with operable primary tumors, chemotherapy was planned to start within 42 days of biopsy, with definitive surgery performed after three cycles. RESULTS: Forty-one patients had operable nonmetastatic limb sarcomas, and 23 (56%) completed six chemotherapy cycles. Limb salvage was possible in 33 patients (80%), and 16 (42%) of 38 assessable specimens showed a good pathologic response (≥ 90% necrosis). Median time to progression was 56 months, and the 5-year progression-free survival rate was 56% (95% confidence interval [CI], 40% to 72%). Median survival time was 63 months, and the 5-year survival rate was 59% (95% CI, 41% to 77%). Patients with a good pathologic response had longer survival times and times to progression than did those with a poor response. Also treated were two patients with locally recurrent and nine with metastatic disease, and these patients had a median survival time of 17.5 months. CONCLUSION: Our study suggests that adjuvant or neoadjuvant chemotherapy with DOX/DDP is beneficial in MFH-B. Good pathologic response rates and survivals are quite comparable with those for osteosarcoma, a related bone tumor for which adjuvant or neoadjuvant chemotherapy is an accepted practice.