bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
Authors: Santoro A , Tursz T , Mouridsen H , Verweij J , Steward W , Somers R , Buesa J , Casali P , Spooner D , Rankin E 
Published: February 2017

PURPOSE The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas. PATIENTS AND METHODS This was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C). RESULTS The overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm A, 51 weeks on arm B, and 55 weeks on arm C). The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens. Cardiotoxicity was also more frequent in this arm, but other toxicities were similar. CONCLUSION In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.
Contralateral breast cancer: annual incidence and risk parameters.
Authors: Broët P , de la Rochefordière A , Scholl S M , Fourquet A , Mosseri V , Durand J C , Pouillart P , Asselain B 
Published: February 2017

PURPOSE To screen for factors that might predict the risk of developing metachronous contralateral breast cancer (CBC), taking into account the influence of local or distant recurrence, and to assess the annual incidence of CBC. PATIENTS AND METHODS Of 4,748 women with invasive unilateral breast cancer, clinical stage I to IIIa, treated between 1981 and 1987, 282 metachronous CBCs were diagnosed. Due to competing risks between the occurrence of CBC and other events, several options for multivariate analysis were considered. RESULTS The median follow-up time was 80 months (range, 1 to 158). The cumulative rate of CBC was 4.1% +/- 0.3% at 5 years, and the annual incidence rate of CBC increased slowly, while the risk of local recurrence and metastases decreased after the fourth year. Whichever model we chose, age less than 55 years (relative risk [RR] = 1.40) at the time of diagnosis of the first breast cancer, as well as the presence of lobular type carcinoma (RR = 1.50), was associated with an increased risk of developing a tumor in the contralateral breast. Adjuvant chemotherapy significantly decreased (RR = 0.54) the risk of CBC. CONCLUSION Lobular histology and age less than 55 years are found to increase the risk of CBC, while adjuvant chemotherapy significantly decreased the risk of CBC. The progressive rise in the annual incidence rates of CBC, together with the absence of a link between clinical prognostic factors of the first cancer and CBC, suggested that CBC can be considered as a second primary breast cancer.
Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study.
Authors: McGuire W P , Hoskins W J , Brady M F , Homesley H D , Creasman W T , Berman M L , Ball H , Berek J S , Woodward J 
Published: February 2017

PURPOSE We report a prospective randomized trial in women with advanced ovarian cancer to evaluate the importance of chemotherapy dose-intensity on survival, progression-free survival (PFS), and response. PATIENTS AND METHODS A total of 485 patients with epithelial ovarian cancer and residual masses more than 1 cm following surgery (stage III presentation) or any stage IV presentation were randomly assigned to receive either standard therapy (cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for eight courses) or intense therapy (cyclophosphamide 1,000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for four courses). Dose modification was rigidly controlled to maintain intensity. Clinical and pathologic responses were assessed, when appropriate, as well as PFS interval and survival. RESULTS A total of 458 patients met all eligibility criteria and were assessed for survival and PFS. The dose-intensive group received the same total dose of cyclophosphamide and cisplatin, but 1.97 times greater dose-intensity than the standard group. Clinical and pathologic response rates; response duration, and survival were similar in both groups of patients. Hematologic, gastrointestinal, febrile episodes, septic events, and renal toxicities were significantly more common and severe in the dose-intensive group. CONCLUSION A doubling of the dose-intensity in the treatment of bulky ovarian epithelial cancers led to no discernible improvement in patient outcome and was associated with more severe toxicity. This study provides no evidence to support the hypothesis that modest increases in dose-intensity without increasing total dose are associated with significant improvement in overall survival or PFS.
T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients.
Authors: Greer J P , Macon W R , Lamar R E , Wolff S N , Stein R S , Flexner J M , Collins R D , Cousar J B 
Published: February 2017

PURPOSE Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy. PATIENTS AND METHODS Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study. RESULTS The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation. CONCLUSION TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas.
Phase I clinical and pharmacokinetic study of topotecan administered by a 24-hour continuous infusion.
Authors: van Warmerdam L J , ten Bokkel Huinink W W , Rodenhuis S , Koier I , Davies B E , Rosing H , Maes R A , Beijnen J H 
Published: February 2017

PURPOSE To determine the maximum-tolerable dose (MTD) and to investigate the pharmacokinetics and pharmacodynamics of topotecan in a phase I study. Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. Broad preclinical activity rationalized further clinical evaluation. PATIENTS AND METHODS In this phase I trial, topotecan was administered by 24-hour continuous infusion every 21 days to patients with solid malignant tumors. RESULTS A total of 25 eligible patients, of whom 22 were pretreated, entered the study. They received the following dosages of topotecan: 2.5, 3.75, 5.60, 8.4, and 10.5 mg/m2 by 24-hour infusion. Reversible leukopenia and thrombocytopenia were dose-limiting, with mild anemia occurring regularly. Other toxicities, such as alopecia, mucositis, nausea, and vomiting were sporadic and mild. Responses were not observed. However, eight patients had stable disease. The plasma concentration-time curves were not compatible with standard linear pharmacokinetic models, and indications were found for the occurrence of nonlinear (saturation) kinetics at the dosages studied. CONCLUSION The recommended dose for phase II studies is 8.4 mg/m2 when administered as a 24-hour infusion, which is well tolerated. Further studies will be necessary to account for the putative nonlinear behavior of the drug.
Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies.
Authors: Uziely B , Jeffers S , Isacson R , Kutsch K , Wei-Tsao D , Yehoshua Z , Libson E , Muggia F M , Gabizon A 
Published: February 2017

PURPOSE The purpose of our studies was to define the maximal-tolerated dose of liposomal doxorubicin (DOX-SL; Liposome Technology Inc, Menlo Park, CA), a doxorubicin formulation of polyethyleneglycol-coated liposomes, characterize the toxicities associated with this formulation, and evaluate any indication of antitumor activity within a phase I setting. PATIENTS AND METHODS Two separate phase I studies were conducted following the initial human pharmacokinetic testing at one of the sites (Hadassah). The starting dose of 20 mg/m2 at the University of Southern California was just below the dose without toxicity in the pharmacokinetic study. At Hadassah, the phase I starting dose was just above their earlier safe single doses, 60 mg/m2. Both studies involved cohorts of at least three patients and redosing every 3 to 4 weeks. To determine the recommended dose for phase II trials, an additional level of 50 mg/m2 every 3 weeks was explored, and the level of 60 mg/m2 every 4 weeks was expanded. RESULTS A total of 56 patients receiving 281 courses of DOX-SL was accrued and evaluated for toxicity. Hand-foot (H-F) syndrome and stomatitis are the two main dose-limiting factors of DOX-SL. Stomatitis was dose-limiting for high single doses of DOX-SL greater than 70 mg/m2. Skin toxicity manifested primarily as H-F syndrome was dose-limiting for repetitive dosing, but acceptable at either 50 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks. Attenuation of acute subjective symptoms and lack of alopecia were generally observed. Patients with carcinomas of the breast, ovary, prostate, and head and neck were among those showing objective antitumor responses or improvement based, in part, on blood levels of tumor markers. CONCLUSION The toxicity profile of DOX-SL differs prominently from that of the free drug administered by bolus or rapid infusion and with some differences, resembles that of prolonged continuous infusion. This finding, as well as the antitumor activity observed, supports wide phase II testing of DOX-SL in solid tumors.
Does knowledge guide practice? Another look at the management of non-small-cell lung cancer.
Authors: Raby B , Pater J , Mackillop W J 
Published: February 2017

PURPOSE To describe Canadian doctors' beliefs about the appropriate role of chemotherapy and radiotherapy in the management of non-small-cell lung cancer (NSCLC). METHODS A mail survey of a random sample of Canadian respirologists, thoracic surgeons, radiation oncologists, and medical oncologists was performed. Three cases of NSCLC were described and respondents were asked to estimate the prognosis in each case and to give their treatment recommendations. RESULTS Responses were obtained from 234 of 330 eligible subjects (74%). Doctors' treatment recommendations varied widely. After a complete resection for stage II NSCLC, 68% recommended no adjuvant treatment, 28% recommended radiotherapy, 1% recommended chemotherapy, and 3% recommended both radiotherapy and chemotherapy. For an asymptomatic patient with stage IIIb NSCLC, 17% recommended no active treatment, 65% recommended radiotherapy alone, 16% recommended radiation and chemotherapy, and 2% recommended chemotherapy alone. For an asymptomatic patient with a stage IV NSCLC, 80% recommended no active treatment and 20% recommended chemotherapy. Doctors' beliefs about the natural history of NSCLC and its response to treatment varied widely. Seventy-five percent of respondents believed that adjuvant radiotherapy did not increase survival in stage II disease, but 25% believed that it did. Thirty percent believed that the addition of chemotherapy to radiotherapy in stage III increased survival, but 70% believed that it did not. Fifty-five percent believed that chemotherapy increased the median survival in stage IV, but 45% believed that it did not. Doctors' beliefs about the efficacy of treatment were strongly associated with their treatment recommendations. CONCLUSION Personal beliefs, rather than universal knowledge, currently guide the management of NSCLC in Canada.
CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors.
Authors: Cannistra S A , Abu-Jawdeh G , Niloff J , Strobel T , Swanson L , Andersen J , Ottensmeier C 
Published: February 2017

PURPOSE CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44S) as well as several CD44 variant isoforms produced through alternative splicing. Expression of CD44 variants is associated with clinically aggressive behavior in some human tumors. The purpose of the present study is to define the expression of CD44 variant isoforms in ovarian cancer and to investigate whether the expression of these molecules is associated with adverse prognosis. MATERIALS AND METHODS Six specimens of normal ovarian surface epithelium (NOSE) and 31 separate cases of newly diagnosed ovarian cancer were studied by a combination of reverse-transcription polymerase chain reaction (RT-PCR) and immunoperoxidase staining. Clinical correlation was made between CD44 variant expression and stage (I/II v III/IV), residual disease (< or = 2.0- v > 2.0-cm mass), age (< or = 65 v > 65 years), histology (papillary serous v other), grade, and survival. RESULTS RT-PCR analysis revealed that NOSE predominantly expressed transcripts for CD44S, as well as a restricted pattern of transcripts characteristic of CD44 splice variants. CD44S and CD44 variant exon nine sequences (CD44-9v) were focally expressed in one of two NOSE specimens examined by immunoperoxidase staining. In comparison, the majority (71%) of ovarian cancer specimens expressed a complex pattern of CD44 splice variants by RT-PCR analysis. Immunoperoxidase studies revealed that the majority of ovarian cancer specimens expressed both CD44S and CD44-9v, whereas expression of sequences from variant exons 3, 4, and 6 was uncommon. There was no association between CD44 variant expression (transcript or protein) and stage, residual disease, age, histology, grade, or survival. CONCLUSION Expression of CD44S and CD44-9v is a common feature of epithelial ovarian cancer cells. The lack of a significant association between CD44 variant expression and prognosis suggests that other factors may be more important in determining the clinical behavior of this disease.
Phase I and pharmacologic studies of pyrazoloacridine, a novel DNA intercalating agent, on single-dosing and multiple-dosing schedules.
Authors: Rowinsky E K , Noe D A , Grochow L B , Sartorious S E , Bowling M K , Chen T L , Lubejko B G , Kaufmann S H , Donehower R C 
Published: February 2017

PURPOSE To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacologic behavior of pyrazoloacridine (PZA), a novel DNA intercalator with a unique mechanism of action, on single- and multiple-dosing schedules. PATIENTS AND METHODS PZA was administered on a single-dosing schedule as a 1- to 3-hour infusion and on a multiple-dosing schedule as a 1-hour infusion daily for 5 days to cancer patients at doses ranging from 400 to 935 mg/m2 and 40 to 180 mg/m2/d every 3 weeks, respectively. RESULTS On the single-dosing 1-hour schedule, CNS toxicity, characterized by neuropsychiatric and neuromotor effects, prompted prolongation of the infusion duration to 3 hours and led to a study of PZA on a multiple-dosing schedule. Both measures resulted in lower incidence of CNS toxicity. Neutropenia was the principal toxicity and precluded dose escalation to levels greater than 750 mg/m2 on the single-dosing (3-hour) schedule and 150 mg/m2/d x 5 (total dose, 750 mg/m2) on the multiple-dosing schedule. Thrombocytopenia, anemia, and nonhematologic effects occurred less frequently. Responses were observed in several patients with platinum- and taxane-refractory ovarian carcinoma; antitumor activity was also noted in patients with cervical and colorectal carcinomas. Significant intraindividual variability characterized by the presence of multiple drug peaks and troughs was observed in the pharmacologic studies. The maximal PZA concentrations achieved in both studies exceeded drug concentrations associated with significant cytotoxicity in preclinical studies and correlated with the occurrence of CNS toxicity. CONCLUSION Neutropenia is the dose-limiting toxicity on both schedules and 750 mg/m2 and 150 mg/m2/d are the recommended starting doses of PZA on single- and multiple-dosing schedules, respectively, for minimally pretreated patients in phase II studies; slightly lower doses are recommended for more heavily pretreated subjects. The favorable toxicity profile of PZA and its antitumor activity in several refractory tumors warrant broad phase II evaluations of this agent.
Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin.
Authors: Abbruzzese J L , Abbruzzese M C , Lenzi R , Hess K R , Raber M N 
Published: February 2017

PURPOSE Diagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed. PATIENTS AND METHODS Data from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test. RESULTS A primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed was superior to that of patients in whom the primary tumor remained unknown. Specific patient subsets contributed most to the improved survival duration of the group in which the primary tumor was found, including lymphoma patients diagnosed solely by pathologic criteria and female patients with primary breast or ovarian cancer. The cost of diagnosis was mostly due to the extensive use of computed tomography. Except for ovarian cancer, computed tomography rarely identified treatable primary tumors. CONCLUSION The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients. Primary malignancies with the best survival can be diagnosed through careful pathologic review and focused evaluations for breast and ovarian cancer in women.
Biology and therapy of pediatric rhabdomyosarcoma.
Authors: Pappo A S , Shapiro D N , Crist W M , Maurer H M 
Published: February 2017

PURPOSE To review key developments in biology and therapy of rhabdomyosarcoma (RMS) since the early 1970s. PATIENTS AND METHODS The literature regarding biology, therapy, and late effects of therapy through March 1995 was reviewed. RESULTS The two major histiotypes, embryonal and alveolar, are characterized by specific genetic abnormalities that provide clues to mechanisms of tumor induction. Alveolar tumors, for example, often possess a chromosomal translocation [t(2;13)(q35;q14)] that fuses the PAX3 gene in band 2q35 with the FKHR gene in band 13q14, creating a novel chimeric protein that could inappropriately activate normal targets of the PAX3 gene product, thereby contributing to tumorigenesis. Recognition of prognostically important patient groups primarily identified by tumor extent, site, and histology, and development of effective risk-based multimodal therapy in randomized trials, have increased long-term survival in RMS from 25% in 1970 to more than 70% in current studies. The most significant recent gain in therapeutic results was realized in patients with gross residual tumor after biopsy. CONCLUSION Contemporary risk-based therapy cures more than two thirds of children with RMS while minimizing acute and late effects. Increased dose-intensity of known effective agents with hematopoietic growth factor support, new agents, and hyperfractionated irradiation are being evaluated in hopes of further improving therapy. Recent discovery of novel genetic features in this tumor should lead to better methods of diagnosis and risk assessment, and ultimately to identification of molecular targets for specific treatment.