bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy Dose-Intensification for Pediatric Patients With Ewing's Family of Tumors and Desmoplastic Small Round-Cell Tumors: A Feasibility Study at St. Jude Children's Research Hospital
Authors: Marina Neyssa M. , Pappo Alberto S. , Parham David M. , Cain Alvida M. , Rao Bhaskar N. , Poquette Catherine A. , Pratt Charles B. , Greenwald Carol , Meyer William H. 
Published: February 2017

PURPOSE: To evaluate the feasibility of dose-intensification for patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell tumors. PATIENTS AND METHODS: From February 1992 to June 1996, we treated 53 consecutive patients on our Ewing's protocol. Induction comprised three cycles of ifosfamide/etoposide on days 1 to 3 and cyclophosphamide (CTX)/doxorubicin on day 5, followed by granulocyte colony-stimulating factor. Local control using surgery and/or radiotherapy started at week 9 along with vincristine/dactinomycin. Maintenance included four alternating cycles of ifosfamide/ etoposide and doxorubicin/CTX, with randomization to one of two CTX dose levels to determine the feasibility of dose-intensification during maintenance. RESULTS: Patients had a median age of 13.4 years (range, 4.5 to 24.9 years); 34 patients were male and 43 patients were white. Nineteen patients presented with metastatic disease, 29 had tumors greater than 8 cm in diameter, and 26 had primary bone tumors. These patients received 155 induction cycles, 91% of which resulted in grade 4 neutropenia, 68% in febrile neutropenia, and 68% in grade 3 to 4 thrombocytopenia. During maintenance, grade 4 neutropenia and grade 3 to 4 thrombocytopenia occurred in 81% and 85% of cycles, respectively. Thirty-five patients (66%) completed all therapy, only 13 without significant delays; three developed secondary myeloid malignancies. The toxicity and time to therapy completion were similar in both CTX arms. Estimated 3-year survival and event-free survival were 72% ± 8% and 60% ± 9%, respectively. CONCLUSION: Although intensifying therapy seems feasible for 25% of patients on this study, toxicity was considerable. Therefore, the noninvestigational use of dose-intensification in patients with EFT should await assessment of its impact on disease-free survival.
Comparison of High-Dose Therapy and Autologous Stem-Cell Transplantation With Conventional Therapy for Hodgkin's Disease Induction Failure: A Case-Control Study
Authors: André Marc , Henry-Amar Michel , Pico José-Luis , Brice Pauline , Blaise Didier , Kuentz Mathieu , Coiffier Bertr , Colombat Philippe , Cahn Jean-Yves , Attal Michel , Fleury Joël , Milpied Noël , Nedellec Gérard , Biron Pierre , Tilly Hervé , Jouet Jean-Paul , Gisselbrecht for the Société Francaise de Greffe de Moelle Christian 
Published: February 2017

PURPOSE: To determine the prognostic factors and outcome of first-line induction failure Hodgkin's disease patients who were treated with a salvage regimen of high-dose chemotherapy and autologous stem-cell transplantation, and to compare them with matched, conventionally treated patients. PATIENTS AND METHODS: We retrospectively analyzed data relating to 86 Hodgkin's disease patients who underwent autologous stem-cell transplantation after failure of the first chemotherapy regimen, either because they did not enter a complete remission and experienced progression of disease less than 3 months after the end of their first-line treatment or because they showed evidence of disease progression during first-line therapy. Graft patients were matched with 258 conventionally treated patients (three controls per case) for age, sex, clinical stage, B symptoms, and time at risk; patient data were obtained from international databases. RESULTS: Among the 86 graft patients, the median age at diagnosis was 29 years (range, 14 to 57 years). Thirty-nine percent of patients had stage II disease, 23% had stage III disease, and 38% had stage IV disease. Seventy percent of the patients received chemotherapy and 30% received combined modality therapy; 60% of the patients received a seven- or eight-drug regimen. After this first-line treatment, 91% had disease progression and 9% had a brief partial response. Eighty patients received a second-line treatment; pretransplantation status was as follows: 24% of patients had a complete remission, 38% had a partial remission (PR), 14% had stable disease, and disease progression occurred in 24%. With a median follow-up of 22 months (range, 4 to 105 months) from diagnosis, the 5-year event-free survival and overall survival rates from transplantation were 25% and 35% (95% confidence intervals, 15 to 36 and 23 to 49), respectively. In multivariate analysis, the pretransplantation disease status after salvage therapy was the only significant prognostic factor for survival (PR: relative risk = 2.8, P = .017; progressive disease: relative risk (RR) = 5.26, P < .001). From diagnosis, the 6-year overall survival rates of the graft patients and 258 matched conventionally treated patients were 38% and 29%, respectively (P = .058). CONCLUSION: Autologous stem-cell transplantation represents the best therapeutic option currently available for patients with primary induction failure and is associated with acceptable toxicity. Response to second-line treatment before high-dose chemotherapy is the only prognostic factor that can be correlated with survival.
Treatment of Patients With Low-Grade B-Cell Lymphoma With the Combination of Chimeric Anti-CD20 Monoclonal Antibody and CHOP Chemotherapy
Authors: Czuczman M. S. , Grillo-López A. J. , White C. A. , Saleh M. , Gordon L. , LoBuglio A. F. , Jonas C. , Klippenstein D. , Dallaire B. , Varns C. 
Published: February 2017

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody, Rituxan (Rituximab, IDEC-C2B8; IDEC Pharmaceuticals Corporation, San Diego, CA), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. PATIENTS AND METHODS: Forty patients with low-grade or follicular B-cell non–Hodgkin's lymphoma received six infusions of Rituxan (375 mg/m2 per dose) in combination with six doses of CHOP chemotherapy. RESULTS: The overall response rate was 95% (38 of 40 patients). Twenty-two patients experienced a complete response (55%), 16 patients had a partial response (40%), and two patients, who received no treatment, were classified as nonresponders. Medians for duration of response and time to progression had not been reached after a median observation time of 29 + months. Twenty-eight of 38 assessable patients (74%) continued in remission during this median follow-up period. The most frequent adverse events attributable to CHOP were alopecia (38 patients), neutropenia (31 patients), and fever (23 patients). The most frequent events attributed to Rituxan were fever and chills, observed primarily with the first infusion. No quantifiable immune response to the chimeric antibody was detected. In a subset of 18 patients, the bcl-2 [t(14;18)] translocation was positive in eight patients; seven of these patients had complete remissions and converted to polymerase chain reaction (PCR) negativity by completion of therapy. CONCLUSION: This is the first report demonstrating the safety and efficacy of Rituxan anti-CD20 chimeric antibody in combination with standard-dose systemic chemotherapy in the treatment of indolent B-cell lymphoma. The clinical responses suggest an additive therapeutic benefit for the combination with no significant added toxicity. The conversion of bcl-2 from positive to negative by PCR in blood and/or marrow suggests possible clearing of minimal residual disease not previously demonstrated by CHOP chemotherapy alone.
Bromodeoxyuridine Alternating With Radiation for Advanced Uterine Cervix Cancer: A Phase I and Drug Incorporation Study
Authors: Eisbruch Avraham , Robertson John M. , Johnston Carolyn M. , Tworek Joseph , Reynolds Kevin R. , Roberts James A. , Lawrence Theodore S. 
Published: February 2017

PURPOSE: Preclinical studies show a significant increase in the ratio of the radiosensitizer bromodeoxyuridine (BUdR) in tumors versus the intestinal mucosa during the drug elimination period, compared with the ratio during drug infusion. We constructed a phase I study in patients with locally advanced cervix cancer, using alternating cycles of BUdR and radiation therapy (RT). PATIENTS AND METHODS: Eighteen patients with stage IIB to IVA cervix cancer participated. A treatment cycle consisted of a 4-day BUdR infusion followed by a week of pelvic RT, 15 Gy twice daily in 1.5-Gy fractions. After three cycles, additional BUdR was infused, followed by brachytherapy. The fraction of thymidine replaced by BUdR and the fraction of cells incorporating BUdR were determined in rectal mucosa and tumor biopsies at the end of the first BUdR infusion (day 5), at the middle of the first RT week (day 10), and at the time of brachytherapy. RESULTS: Dose-limiting toxicity was observed in one of 16 patients receiving 1,000 mg/m2/d × 4 days and inboth patients receiving 1,333 mg/m2/d × 4 days each cycle. After a median follow-up of 39 months, 12 patients (66%) were free of pelvic disease and nine (50%) were alive and disease free. The ratio of tumor to rectum BUdR incorporation averaged 1.5 to 1.8 and did not differ significantly between day 5 and day 10. A trend toward reduced ratio was observed at brachytherapy. Drug-containing cells in rectal biopsies migrated from the crypts to the mucosal surface. CONCLUSION: In this schedule, 1,000 mg/m2/d is the maximum-tolerated dose of BUdR. BUdR incorporation levels in tumors were consistent with clinically significant radiosensitization. The migration of BUdR-containing rectal mucosa cells from the crypts to the surface at the time of RT suggests that this regimen may offer a relative sparing of the mucosa from radiosensitization.
Implementing Guidelines for Cancer Pain Management: Results of a Randomized Controlled Clinical Trial
Authors: Du Pen Stuart L. , Du Pen Anna R. , Polissar Nayak , Hansberry Jennifer , Kraybill Beth Miller , Stillman Mark , Panke Joan , Everly Rebecca , Syrjala Karen 
Published: February 2017

PURPOSE: Pain and symptom management is an integral part of the clinical practice of oncology. A number of guidelines have been developed to assist the clinician in optimizing comfort care. We implemented clinical guidelines for cancer pain management in the community setting and evaluated whether these guidelines improved care. PATIENTS AND METHODS: Eighty-one cancer patients, aged 37 to 76 years, were enrolled onto a prospective, longitudinal, randomized controlled study from the outpatient clinic settings of 26 western Washington–area medical oncologists. A multilevel treatment algorithm based on the Agency for Health Care Policy and Research Guidelines for Cancer Pain Management was compared with standard-practice (control) pain and symptom management therapies used by community oncologists. The primary outcome of interest was pain (Brief Pain Inventory); secondary outcomes of interest were all other symptoms (Memorial Symptom Assessment Scale) and quality of life (Functional Assessment of Cancer Therapy Scale). RESULTS: Patients randomized to the pain algorithm group achieved a statistically significant reduction in usual pain intensity, measured as slope scores, when compared with standard community practice (P < .02). Concurrent chemotherapy and patient adherence to treatment were significant mediators of worst pain. There were no significant differences in other symptoms or quality of life between the two treatment groups. CONCLUSION: This guideline implementation study supports the use of algorithmic decision making in the management of cancer pain. These findings suggest that comprehensive pain assessment and evidence-based analgesic decision-making processes do enhance usual pain outcomes.
Chemotherapy and Bone Marrow Transplantation for Cancer Patients Who Are Also Chronic Hepatitis B Carriers: A Review of the Problem
Authors: Liang Raymond , Lau George K.K. , Kwong Y. L. 
Published: February 2017

In places where hepatitis B virus (HBV) infection is endemic, itis often necessary to give chemotherapy to or perform bone marrowtransplantation for cancer patients who are also chronic HBV carriers.When standard chemotherapy was given to lymphoma patients, elevation ofliver transaminases was observed in nearly half of those who werechronic HBV carriers. Ten percent of them became jaundiced, and theoverall liver-related mortality was about 5%. There is currently noreliable way to predict the severity of HBV reactivation afterchemotherapy. The risk is probably higher when the chemotherapy used issignificantly immunosuppressive and the viral load in the liver ishigh. Different strategies have been used in an attempt to reduce therisk of HBV reactivation after chemotherapy, but they have not beenvery successful. Further studies will be required to determine theimpact of newly available antiviral agents that are active against HBV.Recipients who are carriers of HBV or who receive hepatitis B surfaceantigen (HBsAg)-positive marrow are at increased risk of hepatitisB-related morbidity and mortality after bone marrow transplantation(BMT). There is evidence to suggest that prophylactic use of an activeantiviral agent, such as famciclovir, may result in a significantdecrease in the incidence and severity of HBV reactivation after BMT.Sustained serologic clearance of chronic HBV infection has also beenreported in many HBsAg-positive marrow recipients receiving hepatitis Bsurface antibody-positive marrow from their allogeneic donors. Thereseems to be a transfer of both humoral and cellular immunity againstHBV from donors to recipients.Further prospective studies are required to define the best approach tomanage HBsAg-positive cancer patients receiving chemotherapy or BMT. Itis recommended that all cancer patients be checked for their hepatitisB status before receiving chemotherapy or a bone marrow transplant,especially if they reside in or come from endemic areas of HBVinfection.
B-Cell Chronic Lymphocytic Leukemia: A Bird of a Different Feather
Authors: Caligaris-Cappio Federico , Hamblin Terry J. 
Published: February 2017

PURPOSE: To review the recent major advances in the molecular and cell biology of B-cell chronic lymphocytic leukemia (B-CLL).METHODS: We analyzed the nature of malignant B-CLL B cells and their interactions with the microenvironment.RESULTS: B-CLL is a malignancy of a mantle zone-based subpopulation of anergic, self-reactive, activated CD5+B cells devoted to the production of polyreactive natural autoantibodies. It is the quintessential example of a human malignancy that primarily involves defects in the induction of programmed cell death. An abnormal karyotype is observed in about 50% of patients with B-CLL. Patients with 13q14 abnormalities show heavy somatic mutation and have a benign disease. Trisomy 12 is associated with unmutated VH genes, atypical cellular morphology, and progressive disease. Extended cell survival is further shielded by a kinetic refractoriness likely promoted by abnormalities of the B-cell antigen receptor complex and favored by some cytokines that highlight a reciprocal dialog between malignant B and T cells. Because the tumor cells act as the major accessory cells, the accumulating malignant B-cell population per se is a hurdle to the production of normal antibodies and leads to a progressive and severe hypogammaglobulinemia. Conceivably, in the presence of certain immunoglobulin genes and when the T-cell control becomes deficient, activated malignant B cells may become able to present self-antigens and drive residual normal B cells to produce polyclonal autoantibodies restricted to self-antigens expressed only by blood cells and cause autoimmune cytopenias.CONCLUSION: The distinctiveness of B-CLL B cells explains why B-CLL is different from other B-cell tumors and accounts for the development of immune deficiency and autoimmunity.
Review of the Comparative Pharmacology and Clinical Activity of Cisplatin and Carboplatin
Authors: Go Ronald S. , Adjei Alex A. 
Published: February 2017

PURPOSE: To review the pharmacodynamics, pharmacokinetics, toxicities, and relative clinical activities of cisplatin and carboplatin. Through a search of the MEDLINE database, we identified phase III clinical trials and pharmacologic studies comparing cisplatin and carboplatin published in the English language medical literature from January 1966 to December 1997.RESULTS: Prospective randomized trials comparing cisplatin to carboplatin were identified for ovarian (n = 12), germ cell (n = 4), non–small-cell lung (n = 1), small-cell lung (n = 3), and head and neck (n = 4) cancers. Carboplatin and cisplatin were equally effective in suboptimally debulked ovarian cancer and extensive-stage small-cell lung cancer. One study each showed a trend toward better survival in favor of cisplatin for patients with optimally debulked ovarian and limited-stage small-cell lung cancers. These results were, however, based on subset analyses. In germ cell tumors, carboplatin was inferior because of lower relapse-free survival rates. Cisplatin produced superior response rates and survival in head and neck cancers. There are no published randomized phase III studies of bladder, cervical, endometrial, and esophageal cancers.CONCLUSION: Carboplatin does not possess equivalent activity to cisplatin in all platinum-sensitive tumors. Carboplatin can replace cisplatin in chemotherapy regimens for suboptimally debulked ovarian cancer. Two ongoing studies will address the same question in optimally debulked disease. Carboplatin can also be substituted for cisplatin in the treatment of non–small-cell and extensive-stage small-cell lung cancers. Its role in limited-stage small-cell lung cancer needs to be investigated further. Carboplatin is inferior to cisplatin in germ cell, head and neck, and esophageal cancers. Randomized studies are needed to determine whether carboplatin has equivalent efficacy to cisplatin in bladder, cervical, and endometrial cancers.
Positron Emission Tomography for Evaluating Para-aortic Nodal Metastasis in Locally Advanced Cervical Cancer Before Surgical Staging: A Surgicopathologic Study
Authors: Rose Peter G. , Adler Lee P. , Rodriguez Michael , Faulhaber Peter F. , Abdul-Karim Fadi W. , Miraldi Floro 
Published: February 2017

PURPOSE: Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy. MATERIALS AND METHODS: After 20 mCi of 2-[18F]fluoro-2-deoxy-d-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection. RESULTS: Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P < .001); five of these patients had abnormalities on computed tomographic scans. CONCLUSION: Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease.
First-Line Chemotherapy With Epirubicin, Paclitaxel, and Carboplatin for Advanced Ovarian Cancer: A Phase I/II Study of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group
Authors: du Bois A. , Lück H. J. , Bauknecht T. , Meier W. , Richter B. , Kuhn W. , Quaas J. , Pfisterer J. 
Published: February 2017

PURPOSE: Despite the progress that has been achieved over the years, survival rates in patients with advanced ovarian cancer are still disappointing. New methods to improve the efficiency of first-line chemotherapy are warranted. One method to improve results is to add more non–cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines are among the candidates for incorporation as the “third drug” into first-line regimens for advanced ovarian cancer. PATIENTS AND METHODS: We performed a phase I/II trial with escalating doses of epirubicin (60, 75, and 90 mg/m2) combined with fixed doses of paclitaxel and carboplatin in 27 previously untreated patients with advanced gynecologic malignancies. RESULTS: Dose-limiting toxicity occurred at dose level 2 (75 mg/m2 epirubicin) and consisted of myelosuppression (neutropenia, thrombocytopenia). No dose-limiting, nonhematologic toxicities were observed. The maximum tolerable dose was epirubicin 60 mg/m2 (E) combined with a 3-hour infusion of paclitaxel 175 mg/m2 (T) and carboplatin AUC 5 (Carbo). Preliminary analysis indicated promising activity against ovarian cancer. CONCLUSION: The three-drug combination ET-Carbo, given according to the outlined dose and schedule, should be considered for further phase III evaluation. A randomized German-French intergroup trial comparing ET-Carbo with carboplatin-paclitaxel has already been initiated.
Randomized Phase II Study of High-Dose Paclitaxel With or Without Amifostine in Patients With Metastatic Breast Cancer
Authors: Gelmon K. , Eisenhauer E. , Bryce C. , Tolcher A. , Mayer L. , Tomlinson E. , Zee B. , Blackstein M. , Tomiak E. , Yau J. , Batist G. , Fisher B. , Iglesias J. 
Published: February 2017

PURPOSE: To determine whether the neurotoxicity of paclitaxel 250 mg/m2 given over 3 hours every 3 weeks could be reduced by pretreatment with amifostine 910 mg/m2. Secondary objectives included comparing myelosuppression, myalgias, and response rates of the two groups. PATIENTS AND METHODS: Forty womenwith metastatic breast cancer were randomized to receive either paclitaxel alone (arm 1) or paclitaxel preceded by amifostine (arm 2). All were assessable for toxicity, and 37 were assessable for response. At baseline and after each cycle, all patients completed questionnaires for neurologic symptoms and had standardized neurologic examinations, including objective assessments of power and vibration sense. In addition, standard follow-up assessments for other toxicities and tumor response were undertaken. Changes from baseline after courses 1, 2, and 3 were assessed. The sample size was sufficient to detect a 50% improvement in the expected determination in sensory change. RESULTS: There were no differences observed in any of the measures of neurotoxicity. Other toxicity was similar in arms 1 and 2, including hair loss (95% v 90%), neurosensory changes (100% v 100%), fatigue/lethargy (85% v 90%), myalgia (95% v 90%), and grade 4 neutropenia (47% v 60%). Nausea, vomiting, dizziness, hypotension, and sneezing were more common in the amifostine arm. Response rates (22.2% v 36.8%) and paclitaxel pharmacokinetics were not significantly different. CONCLUSION: There was no protection from paclitaxel-related neurotoxicity or hematologic toxicity in this study. These results suggest that the mechanism of action of paclitaxel-related toxic effects is not amenable to the cytoprotective action of amifostine.