bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Window of Idarubicin in Children With Extraocular Retinoblastoma
Authors: Chantada Guillermo L. , Fandiño Adriana , Mato Gabriel , Casak Sandra 
Published: February 2017

PURPOSE: The aim of this study was to evaluate in an upfront phase II study the response to idarubicin in children with extraocular retinoblastoma. PATIENTS AND METHODS: The starting dose of idarubicin was 15 mg/m2/d (days 1 and 2) weeks 0 and 3. After an interim evaluation, the dose was reduced to 10 mg/m2/d (days 1 and 2) weeks 0 and 3 because of hematopoietic toxicity. Response was evaluated at week 6. RESULTS: At the Hospital JP Garrahan (Buenos Aires, Argentina), 10 patients (five bilateral) were entered onto the study from 1995 to 1998. A total of 19 cycles were administered. Extraocular sites included orbit (n = 10), bone marrow (n = 3), bone (n = 1), lymph node (n = 1), and CNS (n = 1). The response rate was 60% (95% confidence interval, 30% to 90%). One complete response was achieved, in addition to five partial responses, two cases of stable disease, and two cases of progressive disease. All patients with bone marrow involvement achieved complete clearance of tumor cells. The patient with CNS disease had progressive disease. All patients had severe hematopoietic toxicity (grade 4 neutropenia and grade 3/4 thrombocytopenia after most cycles). Other toxicities included grade 2 diarrhea in 30%. No echocardiographic changes were detected. CONCLUSION: Idarubicin is active in extraocular retinoblastoma. The activity of this drug should be explored in future phase III studies.
Paclitaxel Is Safe and Effective in the Treatment of Advanced AIDS-Related Kaposi's Sarcoma
Authors: Gill Parkash S. , Tulpule Anil , Espina Byron M. , Cabriales Suzanne , Bresnahan Jocelyn , Ilaw Miki , Louie Stan , Gustafson Nancy F. , Brown Marilyn A. , Orcutt Christopher , Winograd Benjamin , Scadden David T. 
Published: February 2017

PURPOSE: Liposomal anthracyclines are the present standard treatment for advanced AIDS-related Kaposi's sarcoma (KS). No effective therapies have been defined for use after treatment failure of these agents. A phase II trial was thus conducted with paclitaxel in patients with advanced KS to assess safety and antitumor activity. MATERIALS AND METHODS: A regimen of paclitaxel at a dose of 100 mg/m2 was given every 2 weeks to patients with advanced AIDS-related KS. Patients were treated until complete remission, disease progression, or unacceptable toxicity occurred. RESULTS: Fifty-six patients with advanced AIDS-related KS were accrued. Tumor-associated edema was present in 70% of patients and visceral involvement in 45%. Forty patients (71%) had received prior systemic therapy; 31 of these were resistant to an anthracycline. The median entry CD4+ lymphocyte count was 20 cells/mm3 (range, 0 to 358). A median of 10 cycles (range, 1 to 54+) of paclitaxel was administered. Fifty-nine percent of patients showed complete (n = 1) or partial response (n = 32) to paclitaxel. The median duration of response was 10.4 months (range, 2.8 to 26.7+ months) and the median survival was 15.4 months. The main side effects of therapy were grade 3 or 4 neutropenia in 61% of patients and mild-to-moderate alopecia in 87%. CONCLUSION: Paclitaxel at 100 mg/m2 given every 2 weeks is active and well tolerated in the treatment of advanced and previously treated AIDS-related KS. The median duration of response is among the longest observed for any regimen or single agent reported for AIDS-related KS. Paclitaxel at this dosage and schedule is a treatment option for patients with advanced AIDS-related KS, including those who have experienced treatment failure of prior systemic therapy.
Phase I and Pharmacokinetic Study of Irinotecan Administered as a Low-Dose, Continuous Intravenous Infusion Over 14 Days in Patients With Malignant Solid Tumors
Authors: Herben Virginie M.M. , Schellens Jan H.M. , Swart Martha , Gruia Gabriela , Vernillet Laurent , Beijnen Jos H. , ten Bokkel Huinink Wim W. 
Published: February 2017

PURPOSE: To evaluate the feasibility of administering irinotecan as a continuous intravenous infusion for 14 to 21 days. PATIENTS AND METHODS: Patients with solid tumors refractory to standard therapy received continuous infusions of irinotecan by means of an ambulatory infusion pump. The starting dosage was 12.5 mg/m2/d for 14 days every 3 weeks. After identification of the maximum-tolerated dose for the 14-day infusion schedule, the protocol was amended to prolong the infusion duration to 17 and 21 days. Pharmacokinetics of irinotecan and SN-38 and its glucuronide were determined using high-performance liquid chromatography and noncompartmental modeling. RESULTS: Thirty-three patients received 85+ courses. At the first dose level (12.5 mg/m2/d), cumulative grade 3 or 4 diarrhea and grade 3 or 4 neutropenia occurred in three of five patients. At a dosage of 10 mg/m2/d, 14-day administration resulted in grade 4 diarrhea in two of six patients and one episode of grade 4 vomiting occurred, whereas with 17-day administration, one episode of grade 3 nausea and two episodes of grade 3 or 4 diarrhea were observed in six patients. Increasing the number of days of infusion to 21 days was not feasible because of cumulative diarrhea. Hematologic toxicity was rare. The mean metabolic SN-38 area under the curve/irinotecan area under the curve ratio was 16% ± 6% compared with 3% to 5% after short infusion schedules involving therapeutic dosages. Partial responses were observed in two patients with extraovarian and colorectal cancer. CONCLUSION: The recommended dosage is 10 mg/m2/d for 14 days, repeated every 3 weeks. Enhanced metabolism of irinotecan to SN-38 may explain in part the low recommended dose for this schedule.
Cytokines in Metastatic Renal Cell Carcinoma: Is It Useful to Switch to Interleukin-2 or Interferon After Failure of a First Treatment?
Authors: Escudier Bernard , Chevreau Christine , Lasset Christine , Douillard Jean Yves , Ravaud Alain , Fabbro Michel , Caty Armelle , Rossi Jean Francois , Viens Patrice , Bergerat Jean Pierre , Savary Jacqueline , Négrier Sylvie 
Published: February 2017

PURPOSE: Interleukin-2 (IL-2) and interferon alfa-2a (IFNα2a) have some antitumor activity in metastatic renal cell carcinoma either alone or in combination. To determine whether either of these cytokines might be efficient after failure of the other, we analyzed a series of patients treated with either IL-2 or IFNα2a as second-line treatment after failure of the other cytokine. PATIENTS AND METHODS: We recently performed a large multicenter study to determine the respective efficacy of IL-2, IFNα2a, or combined treatment in renal cell carcinoma. In this study, patients who progressed on the single-arm treatment could receive the other cytokine in a cross-over trial. IL-2 was administered as a continuous intravenous infusion for 5 days (18 × 106 IU/m2/d), and IFNα2a was administered three times weekly at 18 × 106 IU. RESULTS: A total of 113 patients with progressive disease after first-line treatment received either IFNα2a (n = 48) or IL-2 (n = 65). Toxicity during second-line treatment was similar to that observed during first-line treatment. Only four partial responses were observed (one with IFNα2a and three with IL-2). All partial responders had a performance status of 0 and lung metastases. Moreover, three of these four patients had stable disease or had responded to first-line therapy. Only one patient with confirmed disease progression after receiving IL-2 subsequently responded to IFNα2a. CONCLUSION: Cross-over after failure of IL-2 or IFNα2a is poorly efficient in metastatic renal cell carcinoma, especially when progression has been clearly documented.
Chemoradiation and Adjuvant Chemotherapy in Cervical Cancer
Authors: Wong L. C. , Ngan H. Y.S. , Cheung A. N.Y. , Cheng D. K.L. , Ng T. Y. , Choy D. T.K. 
Published: February 2017

PURPOSE: Radiotherapy is the standard treatment for locally advanced cervical cancer, but treatment results remain disappointing, particularly for women with bulky central disease. We investigated the role of concurrent chemoradiation and adjuvant chemotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred twenty patients with bulky stage I, II, and III cervical cancer were randomized to receive either standard pelvic radiotherapy or chemoradiation (epirubicin 60 mg/m2) followed by adjuvant chemotherapy with epirubicin 90 mg/m2 administered at 4-week intervals for five additional cycles. RESULTS: Fifty-nine patients have relapsed, with a median follow-up duration of 77 months. Patients whoreceived epirubicin radiation therapy showed a significantly longer disease-free (P = .03) and cumulative survival (P = .04). Patients who received radiation alone had significantly more distant metastasis than those who received chemoradiation (P = .012). There was no difference in long-term local tumor control (P = .99). CONCLUSION: Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with standard pelvic radiotherapy alone.
High- Versus Standard-Dose Filgrastim (rhG-CSF) for Mobilization of Peripheral-Blood Progenitor Cells From Allogeneic Donors and CD34+ Immunoselection
Authors: Engelhardt Monika , Bertz Hartmut , Afting Matthias , Waller Cornelius F. , Finke Jürgen 
Published: February 2017

PURPOSE: The efficacy of a high- versus a standard-dose filgrastim (recombinant human granulocyte colony-stimulating factor, or rhG-CSF) regimen to mobilize peripheral-blood progenitor cells (PBPCs) for allogeneic transplantation was investigated in 75 healthy donors. PATIENTS AND METHODS: From December 1994 to December 1997, 75 consecutive donors (median age, 38 years; range, 17 to 67 years) were assigned to two different schedules of rhG-CSF for PBPC mobilization. Fifty donors received 24 μg rhG-CSF/kg body weight (BW) divided into two daily subcutaneous injections (two doses of 12 μg, group A), whereas 25 were treated with 10 μg rhG-CSF once daily (group B). Apheresis was started on day 4 in group A and on day 5 in group B. Target CD34+ cell numbers in apheresis products were ≥ 4 × 106/kg recipient BW. RESULTS: Cytokine priming and collection of PBPCs were equally well tolerated in both groups. Significantly higher CD34+ cell numbers in group A with 3.7 × 106/kg recipient BW/apheresis (0.47 × 106/L apheresis) compared with 2 × 106/kg recipient BW/apheresis (0.25 × 106/L apharesis) in group B were obtained (P < .05). Using standard aphereses (median, 9 L), two doses of 12 μg rhG-CSF/kg allowed collection of ≥ 4 × 106/kg CD34+ cells with two aphereses (range, one to three) in group A versus three aphereses (range, one to six) in group B (P < .015). Donor age, sex, and BW influenced the collection of CD34+ cell numbers: in particular, significantly higher apheresis results were obtained in donors younger than 40 years compared with donors older than 40 years of age (P < .05). In 65 CD34+ selection procedures using avidin-biotin immunoabsorption columns (Ceprate SC System, CellPro, Bothell, WA), a median CD34+ purity of 53%, CD34+ recovery of 40%, and the collection of 2 × 106/kg CD34+ cells/selection were achieved. In group A with higher CD34+ cells/kg/apheresis, CD34+ purity, recovery, and cell yields were 60%, 45%, and 2.3 × 106/kg/selection, respectively, as compared with 48%, 31%, and 0.7 × 106/kg in group B (P < .05). CONCLUSION: Our results demonstrate that twice daily rhG-CSF (two doses of 12 μg/kg BM) compared with once daily rhG-CSF (10 μg/kg BW), in addition to being well tolerated, significantly improves PBPC mobilization, allows the collection of higher numbers of CD34+ cells with one or two standard aphereses, and facilitates subsequent selection procedures in healthy allogeneic donors.
Correlation Between Serum Levels of Cardiac Troponin-T and the Severity of the Chronic Cardiomyopathy Induced by Doxorubicin
Authors: Herman Eugene H. , Zhang Jun , Lipshultz Steven E. , Rifai Nader , Chadwick Douglas , Takeda Kazuyo , Yu Zu-Xi , Ferrans Victor J. 
Published: February 2017

PURPOSE: To investigate, over a wide range of cumulative doxorubicin doses, the feasibility of using serum concentrations of cardiac troponin-T (cTnT) as a biomarker for doxorubicin-induced myocardial damage. MATERIALS AND METHODS: Groups of spontaneously hypertensive rats (SHR) were given 1 mg/kg doxorubicin weekly for 2 to 12 weeks. Cardiomyopathy scores were assessed according to the method of Billingham and serum levels of cTnT were quantified by a noncompetitive immunoassay. Myocardial localization of cTnT was studied by immunohistochemical staining and confocal microscopy. RESULTS: Increases in serum levels of cTnT (0.03 to 0.05 ng/mL) and myocardial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of five and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively. All animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions. The average cTnT levels and the cardiomyopathy scores correlated with the cumulative dose of doxorubicin (0.13 v 0.4 ng/mL cTnT and scores of 1.4 v 3.0 in SHR given 6 and 12 mg/kg doxorubicin, respectively). Decreased staining for cTnT was observed in cardiac tissue from SHR receiving cumulative doses that caused only minimal histologic alterations (scores of 1 to 1.5). Staining for cTnT decreased simultaneously with increases in the severity of the cardiomyopathy scores. CONCLUSION: cTnT is released from doxorubicin-damaged myocytes. Measurements of serum levels of this protein seem to provide a sensitive means for assessing the early cardiotoxicity of doxorubicin.
Psychosocial Predictors of Survival in Metastatic Melanoma
Authors: Butow Phyllis N. , Coates Alan S. , Dunn Stewart M. 
Published: February 2017

PURPOSE: Research interest in psychosocial predictors of the onset and course of cancer has been active since the 1950s. However, results have been contradictory and the literature is noted for methodologic weaknesses. In this prospective study, we aimed to systematically obtain data on psychosocial factors associated with human response to illness. PATIENTS AND METHODS: One hundred twenty-five patients with metastatic melanoma completed questionnaires measuring cognitive appraisal of threat, coping, psychologic adjustment, perceived aim of treatment, social support, and quality of life (QOL). Questionnaires were completed, where possible, every 3 months for 2 years after diagnosis. Survival was measured from date of study entry to date of death or was censored at the date of last follow-up for surviving patients. RESULTS: In a multivariate Cox regression analysis of baseline data, which controlled for demographic and disease predictors, the psychologic variables of perceived aim of treatment (P < .001), minimization (P < .05), and anger (P < .05) were independently predictive of survival. Patients who were married (P < .01) and who reported a better QOL (P < .05) also survived longer. CONCLUSION: The prognostic significance of psychologic and QOL scores remained after allowance for conventional prognostic factors. If these associations reflect an early perception by the patient or doctor of disease progression, then measures are at least valuable early indicators of such progression. If psychologic processes have a more direct influence on the course of the underlying illness, then it may be possible to manipulate them for therapeutic effect. We are now conducting a randomized controlled trial of a psychologic intervention to further elucidate these issues.
Randomized Study of CODE Versus Alternating CAV/EP for Extensive-Stage Small-Cell Lung Cancer: An Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group
Authors: Murray Nevin , Livingston Robert B. , Shepherd Frances A. , James Keith , Zee Benny , Langleben A. , Kraut Michael , Bearden James , Goodwin J. Wendall , Grafton Clive , Turrisi Andrew , Walde David , Croft Herbert , Osoba David , Ottaway Jon , Gandara David 
Published: February 2017

PURPOSE: To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC). PATIENTS AND METHODS: Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm. RESULTS: The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P = .006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0.91 years for CAV/EP) were not statistically different. CONCLUSION: The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.
Prospective Randomized Trial of Docetaxel Versus Doxorubicin in Patients With Metastatic Breast Cancer
Authors: Chan Stephen , Friedrichs Kay , Noel Daniel , Pintér Tamàs , Van Belle Simon , Vorobiof Daniel , Duarte Ricardo , Gil Gil Miguel , Bodrogi Istvan , Murray Elizabeth , Yelle Louise , von Minckwitz Gunter , Korec Stefan , Simmonds Peter , Buzzi Franco , González Mancha Rosario , Richardson Gary , Walpole Euan , Ronzoni Monica , Murawsky Michael , Alakl May , Riva Alessandro , Crown John 
Published: February 2017

PURPOSE: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent–containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m2 or doxorubicin 75 mg/m2 every 3 weeks for a maximum of seven treatment cycles. RESULTS: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P = .008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel. CONCLUSION: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.
Predictors of Sexual Health in Women After a Breast Cancer Diagnosis
Authors: Ganz Patricia A. , Desmond Katherine A. , Belin Thomas R. , Meyerowitz Beth E. , Rowland Julia H. 
Published: February 2017

PURPOSE: To identify variables that might be predictive of sexual health (interest, dysfunction, and satisfaction) in a large sample of breast cancer survivors, with a validation conducted in a second, independent sample. PATIENTS AND METHODS: On the basis of a conceptual framework of sexual health in breast cancer survivors, we performed multivariable regression analyses to estimate sexual interest, dysfunction, and satisfaction in both samples. Additional analyses were performed using stepwise regression and recursive partitioning to explore in each sample the relative contributions of the independent variables toward predicting the outcome measures. RESULTS: The models for sexual interest accounted for at least 33% of the variance, and the significant predictors common to the two samples were having a new partner since the diagnosis of breast cancer, mental health score, and body image score. For sexual dysfunction, the models in the two samples explained at least 33% of the variance, and the common significant predictors were vaginal dryness, past chemotherapy use, and having a new partner since diagnosis. The sexual satisfaction models explained at least 27% of the variance, with the common significant predictors being the quality of the partnered relationship and sexual problems in the partner. CONCLUSION: Among the predictors of sexual health, several are mutable (vaginal dryness, emotional well-being, body image, the quality of the partnered relationship, and sexual problems in the partner), and these should be considered for future interventions to address the sexual health and well-being of breast cancer survivors.