bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Selection for Salvage Cryotherapy for Locally Recurrent Prostate Cancer After Radiation Therapy
Authors: Pisters Louis L. , Perrotte Paul , Scott Shellie M. , Greene Graham F. , von Eschenbach Andrew C. 
Published: February 2017

PURPOSE: Our objective was to identify clinical pretreatment factors associated with early treatment failure after salvage cryotherapy. PATIENTS AND METHODS: Between 1992 and 1995, 145 patients underwent salvage cryotherapy for locally recurrent adenocarcinoma of the prostate. Treatment failure was defined as an increasing postcryotherapy serial prostate-specific antigen (PSA) level of more than or equal to 2 ng/mL above the postcryotherapy nadir or as a positive posttreatment biopsy. We evaluated the following factors as predictors of treatment failure: tumor stage and grade at initial diagnosis, type of prior therapy, stage and grade of locally recurrent tumor, number of positive biopsy cores at recurrence, and precryotherapy PSA level. RESULTS: Among patients with a prior history of radiation therapy only, the 2-year actuarial disease-free survival (DFS) rates were 74% for patients with a precryotherapy PSA less than 10 ng/mL and 28% for patients with a precryotherapy PSA more than 10 ng/mL, P < .00001. The DFS rates were 58% for patients with a Gleason score of less than or equal to 8 recurrence and 29% for patients with a Gleason score greater than or equal to 9 recurrence, P < .004. Among patients with a precryotherapy PSA less than 10 ng/mL, DFS rates were 74% for patients with a prior history of radiation therapy only and 19% for patients with a history of prior hormonal therapy plus radiation therapy, P < .002. CONCLUSION: Patients failing initial radiation therapy with a PSA more than 10 ng/mL and Gleason score of the recurrent cancer more than or equal to 9 are unlikely to be successfully salvaged. Patients failing initial hormonal therapy and radiation therapy are less likely to be successfully salvaged than patients failing radiation therapy only.
Treatment of Invasive Thymoma With Single-Agent Ifosfamide
Authors: Highley M. S. , Underhill C. R. , Parnis F. X. , Karapetis C. , Rankin E. , Dussek J. , Bryant B. , Rowland C. , Hodson N. , Hughes J. , Harper P. G. 
Published: February 2017

PURPOSE: To evaluate single-agent ifosfamide in the treatment of invasive thymoma. PATIENTS AND METHODS: Fifteen patients (eight male and seven female) with histologically confirmed invasive thymoma were treated. The median age was 48 years (range, 23 to 76 years). Four patients had stage III disease, seven patients had stage IVa disease, and four patients had stage IVb disease. The most common histologic type was lymphoepithelial. Seven patients had received prior treatment, including one patient who received chemotherapy. Ifosfamide 1.5 g/m2 was given on days 1 to 5, with mesna as a uroprotector. RESULTS: Thirteen patients were assessable for response. Five complete responses (38.5%; 95% confidence interval [CI], 17.7% to 64.5%) and one partial response (7.7%; 95% CI, 1.4% to 33.3%) were seen. The median duration of complete response was 66+ months (range, 25 to 87 months), and the estimated survival rate 5 years after ifosfamide treatment was 57% (SE, 32% to 79%). The most frequent toxicities were nausea, vomiting, and leucopenia, but these were well tolerated. CONCLUSION: Single-agent ifosfamide possesses significant activity against invasive thymoma and is comparable to currently used combination regimens. The inclusion of ifosfamide in combination therapy, particularly in place of cyclophosphamide in regimens such as cisplatin, doxorubicin, and cyclophosphamide, needs to be evaluated.
Irinotecan Combined With Bolus Fluorouracil, Continuous Infusion Fluorouracil, and High-Dose Leucovorin Every Two Weeks (LV5FU2 Regimen): A Clinical Dose-Finding and Pharmacokinetic Study in Patients With Pretreated Metastatic Colorectal Cancer
Authors: Ducreux Michel , Ychou Marc , Seitz Jean-François , Bonnay Marc , Bexon Alice , Armand Jean-Pierre , Mahjoubi Monder , Méry-Mignard Dominique , Rougier Philippe 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose (MTD) and recommended dose of irinotecan (CPT-11) in combination with fluorouracil (5-FU) and leucovorin (LV), using a biweekly LV5FU2 regimen and increasing doses of CPT-11, and to assess the efficacy of this combination in pretreated patients with colorectal cancer (CRC). PATIENTS AND METHODS: All patients had metastatic CRC and a World Health Organization performance status of 0 or 1. CPT-11 was administered over a 90-minute infusion every 2 weeks at a range of dose levels (100, 120, 150, 180, 200, 220, and 260 mg/m2). LV5FU2 was started 1 hour after the end of the biweekly CPT-11 infusion and was also administered on day 2. RESULTS: Fifty-five patients were entered onto this trial; 549 cycles were administered. The MTD was not reached at 260 mg/m2, and a dose level of 300 mg/m2 was added. The MTD as defined in the protocol was not reached at this dose level either, but all patients had cycles delayed and/or required a dose reduction. This dose was deemed to be the MTD. To take into account both the toxicity of and compliance with the biweekly schedule, the recommended CPT-11 dose was established at 180 to 200 mg/m2. Antitumor activity was observed at almost all dose levels, with an objective response rate of 22%. Median time to progression was 6.3 months and overall survival was 15 months. CONCLUSION: The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity. CPT-11 at 180 to 200 mg/m2 in combination with LV5FU2 has been selected as the recommended dose for further studies.
Randomized Phase III Study of Temozolomide Versus Dacarbazine in the Treatment of Patients With Advanced Metastatic Malignant Melanoma
Authors: Middleton M.R. , Grob J.J. , Aaronson N. , Fierlbeck G. , Tilgen W. , Seiter S. , Gore M. , Aamdal S. , Cebon J. , Coates A. , Dreno B. , Henz M. , Schadendorf D. , Kapp A. , Weiss J. , Fraass U. , Statkevich P. , Muller M. , Thatcher N. 
Published: February 2017

PURPOSE: : To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m2/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m2/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.
Randomized Trial of Filgrastim, Sargramostim, or Sequential Sargramostim and Filgrastim After Myelosuppressive Chemotherapy for the Harvesting of Peripheral-Blood Stem Cells
Authors: Weaver Charles H. , Schulman Kevin A. , Wilson-Relyea Barbara , Birch Robert , West William , Buckner C. Dean 
Published: February 2017

PURPOSE: The purpose of this study was to compare the effects of filgrastim, sargramostim, or sequential sargramostim and filgrastim on CD34+ cell yields and morbidity after myelosuppressive mobilization chemotherapy (MC). PATIENTS AND METHODS: One hundred fifty-six patients were randomized to receive filgrastim (n = 51), sargramostim (n = 52), or sargramostim for 5 days followed by filgrastim (n = 53) after MC with either cyclophosphamide and etoposide (n = 75) or paclitaxel and cyclophosphamide (n = 81). RESULTS: Compared with those who received sargramostim, patients who received filgrastim had faster recovery of an absolute neutrophil count of 0.5 × 109/L or greater (a median of 11 v 14 days; P = .0001), with fewer patients requiring RBC transfusions (P = .008), fewer patients with fever (18% v 52%; P = 0.001), fewer hospital admissions (20% v 42%; P = .013), and less intravenous antibiotic therapy (24% v 69%; P = .001). Patients who received filgrastim yielded more CD34+ cells (median, 7.1 v 2.0 × 106/kg/apheresis; P = .0001), and a higher fraction achieved 2.5 × 106 (94% v 78%; P = .021) and 5 × 106 (88% v 53%; P = .001) or more CD34+ cells/kg with fewer aphereses (median, 2 v 3; P = .002) and fewer days of growth-factor treatment (median, 12 v 14; P = .0001). There were no major differences in outcomes between the filgrastim alone and the sequential regimens. After high-dose chemotherapy, patients who had peripheral-blood stem cells (PBSCs) mobilized with filgrastim or the sequential regimen received higher numbers of CD34+ cells and had faster platelet recovery (P = .015), with fewer patients (P = .014) receiving fewer platelet transfusions (P = .001) than patients receiving sargramostim-mobilized PBSCs. CONCLUSION: It was concluded that filgrastim alone or sequential sargramostim and filgrastim were superior to sargramostim alone for the mobilization of CD34+ cells and reduction of toxicities after MC.
Thromboembolic Events During Chemotherapy for Germ Cell Cancer: A Cohort Study and Review of the Literature
Authors: Weijl Nir I. , Rutten Marc F. J. , Zwinderman Aeilko H. , Keizer H. Jan , Nooy Marianne A. , Rosendaal Frits R. , Cleton Frans J. , Osanto Susanne 
Published: February 2017

PURPOSE: To evaluate the risk of major thromboembolic complications in male germ cell cancer patients receiving cisplatin-based chemotherapy and to review the literature on this subject. PATIENTS AND METHODS: One hundred seventy-nine germ cell cancer patients treated between January 1979 and May 1997 in our hospital were analyzed with respect to risk factors for developing thromboembolic events, such as baseline tumor characteristics, prior tumor therapy, administration of cytostatic agents, and the use of antiemetic drugs. The patients were treated with a variety of combination chemotherapy regimens, primarily cisplatin-containing combination regimens. RESULTS: Of the 179 patients, 15 patients (8.4%) were identified who developed a total of 18 major thromboembolic complications in the time period between the start of chemotherapy and 6 weeks after administration of the last cytostatic drug in first-line treatment. Of these 18 events, three (16.7%) were arterial events, including two cerebral ischemic strokes, and 15 (83.3%) were venous thromboembolic events, including 11 pulmonary embolisms. One (5.6%) of the 18 events was fatal. Liver metastases (odds ratio, 4.9; 95% confidence interval, 1.1 to 20.8) and the administration of high doses of corticosteroids (≥ 80 mg dexamethasone per cycle; odds ratio, 3.5; 95% confidence interval, 1.2 to 10.3) as antiemetic therapy were identified as risk factors for the development of major thromboembolic complications. CONCLUSION: Germ cell cancer patients who receive chemotherapy, in particular those who have liver metastases or receive high doses of corticosteroids, are at considerable risk of developing thromboembolic complications.
Filgrastim as an Alternative to Donor Leukocyte Infusion for Relapse After Allogeneic Stem-Cell Transplantation
Authors: Bishop Michael R. , Tarantolo Stefano R. , Pavletic Z. Steven , Lynch James C. , Morris Mary E. , Zacharias Diane , Armitage James O. , Kessinger Anne 
Published: February 2017

PURPOSE: Donor leukocyte infusion (DLI) effectively treats relapse after allogeneic stem-cell transplantation (alloSCT), but the response may require several months and may be associated with significant toxicity. Filgrastim has also been observed to effectively treat leukemic relapse after alloSCT. A retrospective analysis was performed to determine the effectiveness of filgrastim in treating relapses after alloSCT. PATIENTS AND METHODS: Fourteen patients with hematologic malignancies were treated with filgrastim at relapse after alloSCT. Filgrastim was given at 5 mcg/kg/d subcutaneously for 21 consecutive days. Response was evaluated at 7 days after completion of filgrastim. Immunosuppressants, if present, were rapidly tapered to complete discontinuation at the time of relapse. RESULTS: Three patients were not assessable for response because additional therapy was necessary before completion of filgrastim. Six patients (43%) achieved a complete response on an intent-to-treat basis. When response was evaluated based on relapse type, three of four cytogenetic relapses, two of three morphologic relapses, and one of four hematologic relapses achieved a complete remission. Two responses were observed in patients who were completely off of any immunosuppression at the time of relapse. Six patients developed chronic graft-versus-host disease. The event-free and overall survival rates for all 14 patients are 43% and 73%, respectively. CONCLUSION: The use of filgrastim with rapid discontinuation of immunosuppression results in response rates that are similar to results using DLI. Filgrastim could be considered as an alternative or an adjunct to DLI for relapses after alloSCT.
Palliative Effect of Chemotherapy: Objective Tumor Response Is Associated With Symptom Improvement in Patients With Metastatic Breast Cancer
Authors: Geels Paul , Eisenhauer Elizabeth , Bezjak Andrea , Zee Benny , Day Andrew 
Published: February 2017

PURPOSE: Because one of the goals of chemotherapy for metastatic breast cancer is to provide symptom palliation, we were interested in identifying the relationship between tumor shrinkage and improvement in disease-related symptoms. PATIENTS AND METHODS: Three hundred patients enrolled onto a randomized trial of metastatic breast cancer formed the basis of our study. The nine most common baseline symptoms were identified and followed. Changes from baseline (improvement, stable, worsening) were defined using patient responses to a quality-of-life (QoL) questionnaire (the European Organization for Research and Treatment of Cancer EORTC QLQ-C30) as well as using graded toxicity data collected on case report forms (CRFs). The association between symptom improvement and tumor response was assessed using a linear trend test via a logistic regression model. RESULTS: The most commonly reported baseline symptoms were cancer pain in 38% (CRF data) and 81% of patients (QoL data) and tiredness in 26% (CRF data) and 89% (QoL data) of patients. Three symptoms—cancer pain, shortness of breath, and abnormal mood—showed a significant relationship between improvement and objective response, using both CRF and QoL assessments. Constipation, anorexia, and nausea showed a similar trend when QoL data were used but not when CRF information was used. The converse was seen for lethargy. There was no correlation between symptom change and response for cough and insomnia. CONCLUSION: For some symptoms, we found a significant association between symptom improvement and objective tumor regression. In these cases, symptom improvement was greatest in those patients who had complete or partial responses, followed by those with stable disease and then those with progressive disease. Further work in this area will be useful in determining the surrogate value of objective tumor response in identifying the efficacy of palliative chemotherapy.
Paclitaxel, Ifosfamide, and Cisplatin Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Cancer
Authors: Motzer Robert J. , Sheinfeld Joel , Mazumdar Madhu , Bains Manjit , Mariani Tania , Bacik Jennifer , Bajorin Dean , Bosl George J. 
Published: February 2017

PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m2, and cisplatin 100 mg/m2 were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m2; the largest dose was selected for the phase II part of the trial. RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity. CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.
Gemcitabine in the Treatment of Refractory Hodgkin’s Disease: Results of a Multicenter Phase II Study
Authors: Santoro A. , Bredenfeld H. , Devizzi L. , Tesch H. , Bonfante V. , Viviani S. , Fiedler F. , Parra H. Soto , Benoehr C. , Pacini M. , Bonadonna G. , Diehl V. 
Published: February 2017

PURPOSE: To explore the use of gemcitabine for the treatment of patients with relapsing or refractory Hodgkin’s disease. PATIENTS AND METHODS: Eligible patients had measurable disease and more than one previous chemotherapy regimen. Patients previously treated with high-dose chemotherapy with autologous bone marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250 mg/m2, was administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any dose of gemcitabine that could not be given on time was omitted. Patients who had not experienced any hematologic or nonhematologic toxicity after one complete cycle of therapy were permitted to have subsequent doses increased by 20%: that is, from 1,250 mg/m2 to 1,500 mg/m2. RESULTS: Of the 23 enrolled patients, 22 were assessable for response; all 23 patients were included in the efficacy analysis. Disease status for two patients (9%) reached a state of complete remission, and seven patients (30%) achieved a partial response, for an overall response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of achieving a response was not influenced by a patients’ main pretreatment characteristics or by their response to their last prior chemotherapy. The median duration of response was 6.7 months (range, 2 to 33+ months), and the median overall survival time was 10.7 months (range, 4 to 34.7+ months). In general, toxicities were mild; no treatment-related deaths occurred, and only one life-threatening adverse event was reported for this study. CONCLUSION: Gemcitabine was shown to be active in heavily pretreated patients with Hodgkin’s disease, producing a response rate of 39%. Additionally, drug-related toxicities were mild, which thus suggests the possible inclusion of gemcitabine in an earlier phase of treatment.
Locoregional Recurrence Patterns After Mastectomy and Doxorubicin-Based Chemotherapy: Implications for Postoperative Irradiation
Authors: Katz Angela , Strom Eric A. , Buchholz Thomas A. , Thames Howard D. , Smith Cynthia D. , Jhingran Anuja , Hortobagyi Gabriel , Buzdar Aman U. , Theriault Richard , Singletary S. Eva , McNeese Marsha D. 
Published: February 2017

PURPOSE: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation. PATIENTS AND METHODS: A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 116 months. Rates of isolated and total LRR (± distant metastasis) were calculated by Kaplan-Meier analysis. RESULTS: The 10-year actuarial rates of isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three, four to nine, or ≥ 10 involved nodes, respectively (P < .0001). Chest wall (68%) and supraclavicular nodes (41%) were the most common sites of LRR. T stage (P < .001), tumor size (P < .001), and ≥ 2-mm extranodal extension (P < .001) were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with ≥ 10 nodes examined (24% v 11%; P = .02). Patients with tumor size greater than 4.0 cm or extranodal extension ≥ 2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression. CONCLUSION: Patients with tumors ≥ 4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension ≥ 2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.