bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variations in the 5-Hydroxytryptamine Type 3B Receptor Gene as Predictors of the Efficacy of Antiemetic Treatment in Cancer Patients
Authors: Tremblay Pierre-Benoit , Kaiser Rolf , Sezer Orhan , Rösler Nadja , Schelenz Claudia , Possinger Kurt , Roots Ivar , Brockmöller Jürgen 
Published: May 2003

Purpose: Serotonin (5-hydroxytryptamine type 3 [5-HT3]) receptor antagonists have substantially reduced but not eliminated nausea and vomiting in patients undergoing cancer chemotherapy. They act through specific binding to the 5-HT3A, 5-HT3B receptor complex. The 5-HT3B subunit seems to be most important for its functionality. We hypothesized that patients with genetic variations in the 5-HT3B receptor gene might respond differently to antiemetic treatment. Patients and Methods: We included 242 cancer patients on their first day of chemotherapy. Nausea and vomiting were documented before and twice during the chemotherapy using standardized interviews and visual analog scales. We sequenced the entire 5-HT3B receptor gene, including the 5` flanking region and at least a 20–base pair intronic sequence of each intron-exon splice site of all patients. Results: Approximately 30% of all patients suffered from nausea or vomiting. Sequencing of the 5-HT3B receptor gene revealed 13 polymorphisms: two of them were amino acid exchanges (Tyr129Ser, Ala223Thr) and two were deletion variants. In both observation periods, patients homozygous for the −100_−102delAAG deletion variant of the promotor region experienced vomiting more frequently than did all the other patients. Conclusion: A more efficient antiemetic treatment with 5-HT3 receptor antagonists might be possible on a pharmacogenetic basis. However, only a small fraction of the therapeutic failure is explained by the −AAG deletion variant of the 5-HT3B receptor gene. Additional clinical and biochemical studies are needed to confirm the association.
Long-Term Follow-Up of a Prospective Study of Combined Modality Therapy for Stage I–II Indolent Non-Hodgkin’s Lymphoma
Authors: Seymour John F. , Pro Barbara , Fuller Lillian M. , Manning John T. , Hagemeister Fredrick B. , Romaguera Jorge , Rodriguez Maria A. , Ha Chul S. , Smith Terry L. , Ayala Ana , Hess Mark , Cox James D. , Cabanillas Fernando , McLaughlin Peter 
Published: May 2003

Purpose: Standard therapy for patients with stage I–II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients. Patients and Methods: A total of 102 eligible patients with stage I–II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT. Results: The patients’ median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (≥ 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P = .02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P < .0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields. Conclusion: With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.
Potential Role of Platelets in Endothelial Damage Observed During Treatment With Cisplatin, Gemcitabine, and the Angiogenesis Inhibitor SU5416
Authors: Kuenen B.C. , Levi M. , Meijers J.C.M. , van Hinsbergh V.W.M. , Berkhof J. , Kakkar A.K. , Hoekman K. , Pinedo H.M. 
Published: May 2003

Purpose: An increased incidence of thromboembolic events was observed during treatment with cisplatin-gemcitabine plus SU5416 (CG+SU5416), a tyrosine kinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor-1 and -2. Nine thromboembolic events occurred in eight of 19 patients. We performed an analysis of parameters of the coagulation cascade and vessel wall activation. Materials and Methods: Markers for thrombin generation and endothelial cell activation were measured in three patients treated with CG+SU5416, two of whom developed a thromboembolic event. The results were compared with measurements in six patients treated with CG alone, and in 17 patients treated with SU5416 alone. Results: During cycles 1 and 2 of treatment with CG+SU5416, a significant cycle-dependent activation of both the coagulation cascade and endothelial cells occurred, whereas platelet counts decreased. Change in platelet number had a significant negative predictive effect on soluble (s)-E-selectin levels. Significant activation of the coagulation cascade only was observed in the patients treated with CG alone, whereas in patients treated with SU5416 alone, significant endothelial cell activation was observed. Conclusion: We hypothesize that endothelial cells deprived of VEGF after exposure to SU5416 became activated and more susceptible to damage during treatment with CG+SU5416, which was aggravated by a transient decrease in platelets, which are, among other things, carriers of VEGF. These results suggests that VEGF, in addition to being a permeability, proliferation, and migration factor, also is a maintenance and protection factor for endothelial cells, and that platelets may have a role in maintaining vascular integrity.
Therapy-Related Acute Promyelocytic Leukemia
Authors: Beaumont M. , Sanz M. , Carli P.M. , Maloisel F. , Thomas X. , Detourmignies L. , Guerci A. , Gratecos N. , Rayon C. , San Miguel J. , Odriozola J. , Cahn J.Y. , Huguet F. , Vekhof A. , Stamatoulas A. , Dombret H. , Capote F. , Esteve J. , Stoppa A.M. , Fenaux P. 
Published: May 2003

Purpose: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries. Patients and Methods: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients. Results: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin’s lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine–based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years. Conclusion: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II–targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.
High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Children and Adults With Newly Diagnosed Pineoblastomas
Authors: Gururangan Sridharan , McLaughlin Colleen , Quinn Jennifer , Rich Jeremy , Reardon David , Halperin Edward C. , Herndon James , Fuchs Herbert , George Timothy , Provenzale James , Watral Melody , McLendon Roger E. , Friedman Allan , Friedman Henry S. , Kurtzberg Joanne , Vredenbergh James , Martin Paul L. 
Published: May 2003

Purpose: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). Patients and Methods: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. Results: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. Conclusion: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.
Patient Preference for Radiotherapy Fractionation Schedule in the Palliation of Painful Bone Metastases
Authors: Shakespeare Thomas P. , Lu Jiade J. , Back Michael F. , Liang Shen , Mukherjee Rahul K. , Wynne Christopher J. 
Published: May 2003

Purpose: The radiotherapeutic management of painful bone metastases is controversial, with several institutional and national guidelines advocating use of single-fraction radiotherapy. We aimed to determine patient choice of fractionation schedule after involvement in the decision-making process by use of a decision board. Patients and Methods: Advantages and disadvantages of two fractionation schedules (24 Gy in six fractions v 8 Gy in one fraction) used in the randomized Dutch Bone Metastasis Study were discussed with patients using a decision board. Patients were asked to choose a fractionation schedule, to give reasons for their choice, and to indicate level of satisfaction with being involved in decision making. Results: Sixty-two patients were entered. Eighty-five percent (95% confidence interval, 74% to 93%) chose 24 Gy in six fractions over 8 Gy in one fraction (P < .0005). Variables including age, sex, performance status, tumor type, pain score, and paying class were not significantly related to patient choice. Multiple fractionation was chosen for lower re-treatment rates (92%) and fewer fractures (32%). Single-fraction treatment was chosen for cost (11%) and convenience (89%). Eighty-four percent of patients expressed positive opinions about being involved in the decision-making process. Conclusion: Decision board instruments are feasible and acceptable in an Asian population. The vast majority of patients preferred 24 Gy fractionated radiotherapy compared with a single fraction of 8 Gy. These results indicate the need for further research in this important area and serve to remind both clinicians and national or institutional policy makers of the importance of individual patient preference in treatment decision making.
Asian Ethnicity–Related Differences in Gastric Cancer Presentation and Outcome Among Patients Treated at a Canadian Cancer Center
Authors: Gill Sharlene , Shah Amil , Le Nhu , Cook E. Francis , Yoshida Eric M. 
Published: May 2003

Purpose: Differences in stage-stratified survival have been reported between Asian and Western populations with gastric cancer. This study examines differences in presentation and outcomes among Asian and non-Asian patients evaluated and treated at a Canadian institution.Patients and Methods: We reviewed 2,043 patients (159 Asians and 1,884 non-Asians) with gastric adenocarcinoma treated between 1978 and 1997. Overall survival was examined by the Kaplan-Meier method, and multivariable analysis by Cox proportional hazards was used to identify whether Asian ethnicity had independent prognostic significance for survival.Results: Median survival was 13.1 months for Asians and 11.1 months for non-Asians (P = .0016). Asian patients were younger and had a greater proportion of signet ring cell histology but were less likely to have proximal disease. Signet ring cell histology did not adversely affect survival. By multivariable analysis, proximal location, poor differentiation, and extent of disease were independently associated with worse survival. Survival was improved with curative resection, palliative resection, and palliative chemotherapy. Asian ethnicity was not independently associated with survival (hazard ratio, 0.89; 95% confidence interval, 0.74 to 1.08). Although a similar proportion of patients underwent curative resection, an interaction was observed between Asian ethnicity and efficacy of resection, with Asians achieving a greater benefit as compared with non-Asians even when adjusted for age and location.Conclusion: The disparity between Eastern and Western gastric cancer survival is not explained by the hypothesis of ethnicity-related differences in tumor biology. Although it is not an independent predictor of survival, Asian ethnicity is associated with distinct characteristics at presentation and more favorable outcomes after curative surgery.
Superiority of Oxaliplatin and Fluorouracil-Leucovorin Compared With Either Therapy Alone in Patients With Progressive Colorectal Cancer After Irinotecan and Fluorouracil-Leucovorin: Interim Results of a Phase III Trial
Authors: Rothenberg Mace L. , Oza Amit M. , Bigelow Robert H. , Berlin Jordan D. , Marshall John L. , Ramanathan Ramesh K. , Hart Lowell L. , Gupta Sunil , Garay Carlos A. , Burger Brent G. , Le Bail Nathalie , Haller Daniel G. 
Published: May 2003

Purpose: In North America, no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan, bolus fluorouracil (FU), and leucovorin (IFL). Patients and Methods: Patients with metastatic colorectal cancer who progressed after IFL therapy were randomly assigned to bolus and infusional FU and leucovorin (LV5FU2), single-agent oxaliplatin, or the combination (FOLFOX4). This planned interim analysis evaluated objective response rate (RR), time to tumor progression (TTP), and alleviation of tumor-related symptoms (TRS) in an initial cohort of patients. Results: Between November 2000 and September 2001, 463 patients from 120 sites in North America were randomly assigned to treatment. FOLFOX4 proved superior to LV5FU2 in all measures of clinical efficacy. Objective RRs determined by an independent radiology panel were 9.9% for FOLFOX4 versus 0% for LV5FU2 (Fisher’s exact test, P < .0001). Median TTP was 4.6 months for FOLFOX4 versus 2.7 months for LV5FU2 (two-sided, stratified log-rank test, P < .0001). Relief of TRS occurred in 33% of patients treated with FOLFOX4 versus 12% of patients treated with LVFU2 (χ2 test, P < .001). Single-agent oxaliplatin was not superior to LV5FU2 in any measure of efficacy. Patients treated with FOLFOX4 experienced a higher incidence of clinically significant toxicities than patients treated with LV5FU2, but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate. Conclusion: For patients with metastatic colorectal cancer, second-line treatment with FOLFOX4 is superior to treatment with LVFU2 in terms of RR, TTP, and relief of TRS.
Pilot Trial of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Gefitinib Plus Carboplatin and Paclitaxel in Patients With Stage IIIB or IV Non–Small-Cell Lung Cancer
Authors: Miller Vincent A. , Johnson David H. , Krug Lee M. , Pizzo Barbara , Tyson Leslie , Perez Wendy , Krozely Peggy , Sandler Alan , Carbone David , Heelan Robert T. , Kris Mark G. , Smith Robert , Ochs Judith 
Published: May 2003

Purpose: Gefitinib is an oral agent that inhibits the tyrosine kinase of the epidermal growth factor receptor. In phase I trials gefitinib was well tolerated and antitumor activity was seen in pretreated non–small-cell lung cancer (NSCLC) patients. Preclinical studies indicated enhanced effects when gefitnib was added to carboplatin or paclitaxel. This pilot trial combined gefitinib with carboplatin and paclitaxel to define the toxicities of the combination and assess drug-drug interactions in untreated advanced NSCLC patients. Patients and Methods: Initially (part 1) patients were randomly assigned to receive intermittent gefitinib with cycle 1 or 2 of chemotherapy. Thereafter (part 2), the highest dose of gefitinib that was given without dose-limiting toxicity (DLT) from part 1 was administered continuously beginning with the first cycle of chemotherapy. Three sequentially enrolled cohorts received gefitinib 250 and 500 mg (intermittently) and 500 mg (continuously). Results: We treated 24 patients; nine patients with 250 mg and 15 patients with 500 mg (nine patients continuous). Two occurrences of DLT were observed. One patient (500 mg, part 1) developed grade 3 rash and another patient (part 2) developed prolonged neutropenia. Steady-state gefitinib levels did not affect exposure to chemotherapy. In a limited sample, chemotherapy modestly increased the gefitinib area under concentration-time curve at steady-state and minimum steady-state trough concentration. Partial responses were observed in five of 24 patients. The median survival was 8 months. Conclusion: The gefitinib with carboplatin and paclitaxel regimen was generally well tolerated and no unanticipated toxicities or clinically relevant pharmacokinetic interactions were observed. Both doses of gefitinib were believed to be safe for further study with chemotherapy. This regimen was thus tested in a completed randomized phase III trial.
Topotecan Is an Active Agent in the First-Line Treatment of Metastatic or Recurrent Endometrial Carcinoma: Eastern Cooperative Oncology Group Study E3E93
Authors: Wadler Scott , Levy Donna E. , Lincoln Sarah T. , Soori Gamini S. , Schink Julian C. , Goldberg Gary 
Published: May 2003

Purpose: To determine the clinical activity and the toxicity profile of the topoisomerase-I inhibitor, topotecan, in women with recurrent or advanced endometrial carcinoma. Patients and Methods: A prospective, phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG). Patients had histologically confirmed advanced or recurrent endometrial carcinoma, measurable disease, no prior cytotoxic therapy, an ECOG performance status of 0 to 2, and evidence of disease progression while on progestins or after radiation therapy. Topotecan was administered at 1.5 mg/m2 (or 1.2 mg/m2 for patients with prior pelvic radiation) intravenously daily for 5 days every 3 weeks. Results: A total of 44 patients were enrolled; 42 were eligible. The study was suspended because of unexpected toxicities, primarily sepsis and bleeding. After toxicity review, the study was reopened using lower doses of topotecan (1.0 mg/m2 or 0.8 mg/m2 for patients with prior radiation therapy). In addition, prophylactic use of growth factors was allowed after the first cycle, and patients with performance status of 2 were excluded. The major toxicities were hematologic and gastrointestinal. Among the 40 assessable patients, there were three (7.5%) complete responders and five partial responders (12.5%), for an overall response rate of 20%. The median duration of response was 8.0 months and of overall survival was 6.5 months. Conclusion: Topotecan is an active agent for the treatment of advanced endometrial carcinoma. At the doses and schedules initially used, toxicities were unacceptable; however, at the modified doses, toxicities were acceptable and clinical activity was preserved.
Metastatic Melanoma in Pregnancy: Risk of Transplacental Metastases in the Infant
Authors: Alexander April , Samlowski Wolfram E. , Grossman Douglas , Bruggers Carol S. , Harris Ronald M. , Zone John J. , Noyes R. Dirk , Bowen Glen M. , Leachman Sancy A. 
Published: May 2003

Purpose: Although metastases to the fetus via the placenta are rare, melanoma is the most common culprit. When it occurs, maternally derived melanoma metastasis in the infant is almost invariably fatal. Patients and Methods: This article reviews current guidelines for placental evaluation in pregnant women with metastatic melanoma and presents surveillance recommendations for their infants. Comprehensive literature reviews were performed on melanoma in pregnancy and melanoma metastasis to the placenta and fetus. The use of interferon alfa in the pediatric population was also reviewed. A comprehensive search of the MEDLINE database (1966 to 2002) was performed. Articles were reviewed and additional references were obtained from the bibliographies. Translation of non-English articles was performed, and authors of previous publications were contacted. Results: Eighty-seven patients with placental or fetal metastasis were identified. Twenty-seven occurrences were attributed to melanoma (31%). The fetus was affected in six of 27 melanoma patients (22%), with five of six infants dying of disease. The use of high-dose interferon alfa adjuvant therapy in pediatric patients has not been reported. Conclusion: The placentas of women with known or suspected metastatic melanoma should be carefully examined grossly and histologically by pathologists. With placental involvement, fetal risk of melanoma metastasis is approximately 22%. Neonates delivered with concomitant placental involvement should be considered a high-risk population. The risk-benefit ratio of adjuvant treatment for a potentially affected infant should be carefully weighed.