bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of paclitaxel by 24-hour continuous infusion for relapsed non-Hodgkin's lymphomas: Southwest Oncology Group trial 9246.
Authors: Press O W , LeBlanc M , O'Rourke T J , Gagnet S , Chapman R A , Balcerzak S P , Fisher R I 
Published: February 2017

PURPOSE The Southwest Oncology Group (SWOG) recently conducted a multiinstitutional phase II trial to determine the complete response (CR) and partial response (PR) rates, toxicities, and progression-free and overall survivals of patients with relapsed non-Hodgkin's lymphomas (NHLs) treated with a 24-hour continuous infusion of paclitaxel at a dose of 175 mg/m2. PATIENTS AND METHODS Sixty-six patients with relapsed NHL who had received minimal prior therapy (one prior chemotherapy regimen for intermediate- to high-grade NHL [44 patients] or one or two prior regimens for low-grade NHL [22 patients]) were premedicated with dexamethasone, diphenhydramine, and cimetidine and then treated with continuous intravenous infusion paclitaxel over 24 hours every 21 days. RESULTS Eleven of 66 patients (17%) achieved rigorously documented objective remissions, including two CRs (3%) and nine PRs (14%). In addition, another five patients (8%) achieved apparent PRs on a single computed tomographic (CT) scan. Responses were brief, lasting a median of 3 months (5 months for indolent lymphomas and 3 months for intermediate- to high-grade lymphomas). Grade 4 or 5 granulocytopenia was the only common serious toxicity, and occurred in 42 of 66 patients (64%). CONCLUSION Paclitaxel is generally well tolerated when given as a continuous infusion of 175 mg/m2 over 24 hours, despite predictable granulocytopenia. However, single-agent paclitaxel has modest clinical efficacy compared with other available treatments for relapsed NHL.
Phase II trial of fludarabine monophosphate in patients with mantle-cell lymphomas.
Authors: Decaudin D , Bosq J , Tertian G , Nedellec G , Bennaceur A , Venuat A M , Bayle C , Carde P , Bendahmane B , Hayat M , Munck J N 
Published: February 2017

PURPOSE The aim of this phase II trial was to assess the efficacy of fludarabine monophosphate in untreated and pretreated mantle-cell lymphomas (MCL). PATIENTS AND METHODS Fifteen patients with MCL were included in the study. In two cases, fludarabine was the first-line therapy, the second in four cases, the third in five cases, and the fourth in four cases. The diagnosis of MCL was based on the criteria of the European Lymphoma Task Force (ELTF), with morphologic, immunologic, and cytogenetic data. Patients were treated with intravenous fludarabine 25 mg/m2/d for 5 days every 4 weeks. RESULTS Toxicity of fludarabine was mild: World Health Organization (WHO) grade 3 and 4 granulocytopenia occurred in 15 of 56 assessable cycles (cy) (27%), there was no grade 3 or 4 thrombocytopenia, one grade 3 bacterial lung infection, and no treatment-related death. There were five partial responses (33%) but no complete response. The duration of these responses was short and ranged from 4 to 8 months. CONCLUSION These results suggest that fludarabine can be moderately effective in the treatment of MCL. Fludarabine appears to be far less effective than in chronic lymphocytic leukemia (CLL) and follicular non-Hodgkin's lymphoma (NHL). Therefore, fludarabine should be evaluated in association with other chemotherapeutic agents in MCL.
Evaluation of topotecan in resistant and relapsing multiple myeloma: a Southwest Oncology Group study.
Authors: Kraut E H , Crowley J J , Wade J L , Laufman L R , Alsina M , Taylor S A , Salmon S E 
Published: February 2017

PURPOSE Topotecan is a topoisomerase I inhibitor with antitumor activity against hematologic and solid tumor malignancies. We evaluated its activity in refractory and relapsing multiple myeloma patients who had received one prior chemotherapeutic regimen. PATIENTS AND METHODS Toptecan 1.25 mg/m2/d was administered as a 30-minute infusion for 5 days repeated every 3 weeks. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d subcutaneously was administered after the first course of treatment if neutropenia was dose-limiting. RESULTS Forty-six patients entered the study, with 43 patients eligible. The major toxicity was granulocytopenia with grade 3 or better occurring in 40 of 43 patients treated; 21 of 43 patients developed grade 3 or greater thrombocytopenia. Other significant toxicity included mild nausea in 23 patients and mild vomiting in 13 patients. The overall response rate (partial response or better) was 16% (95% confidence interval, 7% to 31%), with responses occurring in both relapsed and refractory patients. Responses have lasted 70 to 477+ days, with a median progression-free survival duration of 13 months and median survival time of 28 months. CONCLUSION Topotecan has activity in refractory and relapsing multiple myeloma. Future investigation of topotecan in multiple myeloma including combination therapy and the study of other topoismerase I inhibitors is warranted.
Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group.
Authors: Berenson J R , Lichtenstein A , Porter L , Dimopoulos M A , Bordoni R , George S , Lipton A , Keller A , Ballester O , Kovacs M , Blacklock H , Bell R , Simeone J F , Reitsma D J , Heffernan M , Seaman J , Knight R D 
Published: February 2017

PURPOSE To determine the efficacy and safety of 21 monthly cycles of pamidronate therapy in patients with advanced multiple myeloma. PATIENTS AND METHODS Patients with stage III myeloma and at least one lytic lesion received either placebo or pamidronate 90 mg intravenously administered as a 4-hour infusion monthly for 21 cycles. At study entry, the patients were stratified according to whether they were to receive first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy. Skeletal events (pathologic fracture, radiation or surgery to bone, and spinal cord compression) and hypercalcemia were assessed monthly. RESULTS The results of the first nine previously reported cycles are extended to 21 cycles. Of the 392 randomized patients, efficacy could be evaluated in 198 who received pamidronate and 179 who received placebo. After 21 cycles, the proportion of patients who developed any skeletal event was lower in the pamidronate-group (P = .015). The mean number of skeletal events per year was less in the pamidronate-group (1.3) than in placebo-treated patients (2.2; P = .008). Although survival was not different between the pamidronate-treated group and placebo patients overall, stratum 2 patients who received pamidronate lived longer than those who received placebo (14 v 21 months, P = .041). Pamidronate was safe and well tolerated during the 21 cycles of therapy. CONCLUSION Long-term monthly infusions of pamidronate as an adjunct to chemotherapy are superior to chemotherapy alone in reducing skeletal events in stage III multiple myeloma patients, and may improve the survival of patients on salvage therapy.
Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide.
Authors: Goren M P , Anthony L B , Hande K R , Johnson D H , Brade W P , Frazier M W , Bush D A , Li J T 
Published: February 2017

PURPOSE To compare the pharmacokinetics of the approved I.V. (intravenous) mesna regimen and an investigational I.V.-oral regimen that could be used in outpatients who receive ifosfamide. PATIENTS AND METHODS The I.V. regimen consisted of three I.V. mesna doses given at 0, 4, and 8 hours after ifosfamide administration. The investigational regimen included an I.V. mesna dose given concurrently with ifosfamide, followed 2 and 8 hours later by oral administration of mesna tablets. I.V. and oral mesna doses equaled 20% and 40%, respectively, of the ifosfamide dose. The study subjects were 12 lung cancer patients who received ifosfamide 1.2 g/m2 daily for 5 days. The patients were randomized to receive either the I.V.-oral or I.V. mesna regimen on day 1, followed by crossover to the other regimen on days 2 through 5 of ifosfamide treatment. The urinary profiles of mesna and dimesna excretion were determined on days 1, 2, and 5; pharmacokinetic parameters for blood samples were determined only on day 5. RESULTS During the first 12 hours after ifosfamide administration, the amount of mesna excreted and the profile of urinary mesna excretion was similar for both regimens; however, the I.V.-oral regimen showed less fluctuation in the excretion rate and higher trough values. During hours 12 to 24, about eightfold more mesna was excreted by patients given the I.V.-oral than the I.V. regimen. CONCLUSION These pharmacokinetic data show that the I.V.-oral regimen should be at least as uroprotective as the I.V. mesna regimen. Patients may also benefit from the I.V.-oral regimen because of the higher trough values during hours 0 through 12 and the sustained urinary mesna excretion during hours 12 through 24.
Primary mediastinal nonseminomatous germ cell tumors: results of modern therapy including cisplatin-based chemotherapy.
Authors: Fizazi K , Culine S , Droz J P , Kramar A , Théodore C , Ruffié P , Le Chevalier T 
Published: February 2017

PURPOSE Primary mediastinal nonseminomatous germ cell tumors (NSGCT) are uncommon neoplasms and clinically and biologically distinct from other germ cell tumors (GCT). We describe the clinical and biologic features of these patients and evaluate the results of treatment during the cisplatin era. PATIENTS AND METHODS Between 1976 and 1993, 38 patients with mediastinal NSGCT received cisplatin-based chemotherapy as part of their primary treatment. Twenty-nine of them were initially treated at the Institut Gustave-Roussy (IGR), VillejuiF, France, and nine were referred for salvage treatment. RESULTS Of the 29 patients initially treated at IGR, 11 (39%) had metastasis. A complete response (CR) to therapy was obtained in 19 of 29 patients (66%) after chemotherapy and surgery. Ten patients (34.5%) have remained free of disease with a median follow-up of 89 months. All patients who did not achieve a CR died of disease. The 2-year overall survival rate for the IGR patients is 45% and the 2-year disease-free survival is 37%. Only the presence of extrapulmonary metastasis was of prognostic significance in the univariate analysis (P = .0095). None of the 20 patients who required salvage therapy is currently disease-free. Five patients developed and subsequently died of a hematologic malignancy at an interval range of 1 to 47 months from treatment of mediastinal NSGCT. Cytogenetic analysis of leukemic cells found an isochromosome of the short arm of chromosome 12 (12p) in two cases. The incidence of leukemia was 21% in patients who attained a CR. CONCLUSION Primary mediastinal NSGCT is a clinical and biologic entity that should be distinguished from other GCT. About 40% of these patients can envisage long-term survival with modern therapy that includes cisplatin-based chemotherapy followed by surgical resection of residual masses. New strategies are required for patients who do not attain a CR. Predictive factors and improvement in therapy are required for mediastinal NSGCT-associated leukemia.
Assuring the optimal use of serotonin antagonist antiemetics: the process for development and implementation of institutional antiemetic guidelines at Memorial Sloan-Kettering Cancer Center.
Authors: Nolte M J , Berkery R , Pizzo B , Baltzer L , Grossano D , Lucarelli C D , Kris M G 
Published: February 2017

PURPOSE The need to foster the appropriate and cost-effective use of serotonin-antagonist antiemetic drugs spurred the creation of guidelines. The process by which institution-wide guidelines at Sloan-Kettering were developed, implemented, assessed, and modified is described. METHODS A multidisciplinary group working with disease-specific management teams assigned the emetic potential of chemotherapy programs to one of five categories. Antiemetic regimens, including a specified dose and schedule of a serotonin-antagonist and dexamethasone, were assigned to each emetic category. The information was collated by disease site and chemotherapy program into hospital-wide antiemetic regimen recommendations. Quality assessment was conducted initially and repeated each time the guidelines were modified. RESULTS Patient surveys demonstrated a high level of satisfaction with emetic control, which was similar to reported results. Data from the latest survey showed zero emetic episodes in 93% and 87% of participants given moderate and highly emetogenic chemotherapy, respectively. Compliance with the guidelines, initially in 73%, has been improved using a standardized chemotherapy order "check box" labeled, "Antiemetics as per Guidelines." Antiemetic drug expenditures decreased from a projected $2.8 million to $1.3 million annually. CONCLUSION The guidelines became an educational tool that ensured the delivery of optimal antiemetic therapy chosen by professionals with the greatest knowledge of both the particular chemotherapy regimen and cancer site. Implementation of the guidelines resulted in substantial savings while treating more patients. The guidelines were easily modified as new chemotherapeutic agents and antiemetic drugs became available.
Does tamoxifen cause cancer in humans?
Authors: Stearns V , Gelmann E P 
Published: February 2017

PURPOSE To review the preclinical and clinical data on the carcinogenic potential of tamoxifen. DESIGN A MEDLINE search on the carcinogenicity of tamoxifen was conducted and the literature reviewed. RESULTS Because tamoxifen has estrogen-like effects on some tissues, such as the human uterus, there has been concern that tamoxifen could promote endometrial cancers in women on chronic tamoxifen therapy. Observations in some randomized trials of adjuvant tamoxifen therapy are consistent with a small, but real, increased risk of endometrial cancer in women who take tamoxifen. Since increased endometrial cancer incidence has not been observed in all studies of chronic tamoxifen therapy, there may be an element of detection bias. Laboratory studies have demonstrated that tamoxifen is hepatocarcinogenic in laboratory rats, but not in other species. This carcinogenicity in rats has been linked to the formation of DNA adducts. CONCLUSION The incidence of endometrial cancer is increased in women who take tamoxifen. The data suggest that tamoxifen might be a tumor promoter in human endometrium. However, on the basis of the number of tumors seen by endometrial sampling of tamoxifen-treated women, the impact of tamoxifen as a tumor promoter is small. Women on chronic tamoxifen therapy should have routine annual gynecologic examinations and receive endometrial sampling only in the event of uterine bleeding. Unlike the data in rats, there is no conclusive evidence to link tamoxifen with an increased rate of hepatocellular cancer in humans; the contrasting carcinogenic potential may be attributed to substantial interspecies differences in the metabolism of tamoxifen.
High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma.
Authors: Ayash L J , Elias A , Ibrahim J , Schwartz G , Wheeler C , Reich E , Lynch C , Warren D , Shapiro C , Richardson P , Hurd D , Schnipper L , Frei E , Antman K 
Published: February 2017

PURPOSE Women with locally unresectable and inflammatory breast carcinoma (IBC) have an approximately 30% 5-year disease-free survival (DFS) rate with conventional multimodality therapy. A short but dose-intensive multimodality phase II trial was designed in an attempt to improve outcome in stage IIIB disease. Mastectomy was performed after high-dose therapy to evaluate pathologic response to treatment. METHODS Women with newly diagnosed disease received four 2-week cycles of doxorubicin 90 mg/m2 with granulocyte colony-stimulating factor (G-CSF), followed by cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) with marrow and peripheral-blood progenitor cell (PBPC) support. Local therapy consisted of mastectomy and radiotherapy. Tamoxifen (5 years) was begun if the patient was estrogen receptor-positive (ER+). RESULTS Fifty women (46 stage IIIB [91% IBC], four stage IIIA) entered the study and 47 are assessable. Ten had mastectomy before any systemic therapy (seven with pathologic IBC, three with residual tumor after mastectomy). Eighty percent received full-dose doxorubicin with 60% on schedule. Clinical response rates to induction were 15% complete response (CR), 5% very good partial response (VGPR), 59% partial response (PR), and 21% minor response (MR)/stable disease (SD). Mastectomy after CTCb in 37 patients showed a 14% pathologic CR rate, 29% microscopic foci in breast and/or axilla, and 57% gross tumor. Fifteen (32%) patients have relapsed (median, 17 months post-CTCb). The 30-month DFS is estimated at 64%. For those in pathologic CR, with microscopic, or with gross disease remaining after CTCb, the 30-month DFS is estimated at 100%, 70%, and 38%, respectively. Those with zero, one to three, or > or = four positive nodes at axillary dissection had a median DFS of 31, 18, and 13 months, respectively. CONCLUSION This short but dose-intensive multimodality approach for stage IIIB breast carcinoma is feasible with encouraging results to date.
Secondary myelodysplasia and acute leukemia in breast cancer patients after autologous bone marrow transplant.
Authors: Laughlin M J , McGaughey D S , Crews J R , Chao N J , Rizzieri D , Ross M , Gockerman J , Cirrincione C , Berry D , Mills L , Defusco P , LeGrand S , Peters W P , Vredenburgh J J 
Published: February 2017

PURPOSE To determine the incidence of myelodysplasia (MDS) and/or acute leukemia (AL) in breast cancer patients after high-dose chemotherapy (HDC) with a single conditioning regimen and autologous bone marrow transplant (ABMT), and analyze the cytogenetic abnormalities that arise after HDC. PATIENTS AND METHODS We retrospectively reviewed the records of 864 breast cancer patients who underwent ABMT at Duke University Medical Center, Durham, NC, from 1985 through 1996 who received the same preparative regimen of cyclophosphamide 1,875 mg/m2 for 3 days, cisplatin 55 mg/m2 for 3 days, and BCNU 600 mg/m2 for 1 day (CPB). Pretransplant cytogenetics were analyzed in all patients and posttransplant cytogenetics were evaluated in four of five patients who developed MDS/AL. RESULTS Five of 864 patients developed MDS/AL after HDC with CPB and ABMT. The crude cumulative incidence of MDS/AL was 0.58%. The Kaplan-Meier curve shows a 4-year probability of developing MDS/AL of 1.6%. Pretransplant cytogenetics performed on these five patients were all normal. Posttransplant cytogenetics were performed on four of five patients and they were abnormal in all four, although only one patient had the most common cytogenetic abnormality associated with secondary MDS/AL (chromosome 5 and/or 7 abnormality). CONCLUSION Whereas MDS/AL is a potential complication of HDC with CPB and ABMT, the incidence in this series of patients with breast cancer was relatively low compared with that reported in patients with non-Hodgkin's lymphoma who underwent ABMT. The cytogenetic abnormalities reported in this group of breast cancer patients were not typical of those seen in prior reports of secondary MDS/AL and appear to have occurred after HDC.
Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.
Authors: Grau J J , Estapé J , Fuster J , Filella X , Visa J , Terés J , Soler G , Albiol S , García-Valdecasas J C , Grande L , Bombí J , Bordas J , Alcobendas F 
Published: February 2017

PURPOSE We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.
Reduced integrin alpha3 expression as a factor of poor prognosis of patients with adenocarcinoma of the lung.
Authors: Adachi M , Taki T , Huang C , Higashiyama M , Doi O , Tsuji T , Miyake M 
Published: February 2017

PURPOSE We investigated the possible association between integrin alpha3 and motility-related protein (MRP-1), cluster of differentiation antigen 9 (CD9) gene expression in non-small-cell lung cancer (NSCLC) and evaluated the prognostic significance of integrin alpha3 expression. PATIENTS AND METHODS We performed a retrospective study of integrin alpha3 and MRP-1/CD9 expression in resected tumor tissues from 151 NSCLC patients using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS The ratio of integrin alpha3/beta-actin expression ranged from 0 to 5.87 (mean was 0.80; median, 0.70). Using the cutoff value of 0.7, there were 78 (52%) integrin alpha3-positive tumors and 73 (48%) tumors with reduced integrin alpha3 expression. The immunohistochemical results agreed well with those of the RT-PCR assays, and 88% had no discrepancy. In case of discrepancy, the results of RT-PCR were used in specimen classification. Integrin alpha3 gene expression was independent from MRP-1/CD9 gene expression. No significant association was found between integrin alpha3 expression and the patients' clinical characteristics. The overall survival rate of patients with integrin alpha3-positive NSCLCs was only slightly better than that of individuals whose tumors had reduced integrin alpha3 expression (55.9% v 47.1%; P = .085). By comparison, the overall survival rate of patients with integrin alpha3-positive adenocarcinomas was strikingly greater than in those whose tumors had reduced gene expression (54.4% v 35.2%; P = .004). Multivariate analysis with the Cox regression model of NSCLC and adenocarcinoma indicated that integrin alpha3 expression correlated better (P = .0188 and P = .0008, respectively) with the overall survival rate than other variables, except lymph node status. CONCLUSION No significant association was found between integrin alpha3 and MRP-1/CD9 gene expression in lung cancer. However, reduced integrin alpha3 expression is a poor prognosis factor in patients with adenocarcinomas.