bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical activity of chronic oral etoposide in previously treated metastatic breast cancer.
Authors: Martín M , Lluch A , Casado A , Santabárbara P , Adrover E , Valverde J J , López-Martín J A , Rodriguez-Lescure A , Azagra P , García-Conde J 
Published: February 2017

PURPOSE This study was undertaken to assess the antitumor activity and tolerance of chronic oral etoposide (50 mg/m2/d for 21 days every 4 weeks) in metastatic breast cancer (MBC). PATIENTS AND METHODS Forty-three consecutive metastatic breast cancer patients with at least one site of measurable disease entered the study. All patients had received prior chemotherapy (adjuvant, three patients; adjuvant plus chemotherapy for metastases, 21; chemotherapy for metastases, 19). Twenty-two and 21 patients had also received prior hormonal and radiation therapy, respectively. RESULTS Thirty-five percent of patients (15 of 43; 95% confidence interval, 21% to 51%) had objective responses, according to an intention-to-treat analysis. Responses were seen in lymph nodes (six of 14), skin and soft tissues (eight of 16), lung (six of 14), lytic lesions of the bone (two of six), liver (four of 23), and peritoneum (one of one). The median duration of response was 7 months (range, 3+ to 12). The main toxic side effects were leukopenia (overall, 65% of patients; World Health Organization [WHO] grade 4, 21%), thrombocytopenia (21%; WHO grade 4, 5%) and anemia (51%; WHO grade 4, 5%). Nine patients (21%) required a 25% dose reduction because of myelosuppression, and one patient abandoned treatment because of gastrointestinal toxicity and severe asthenia. Ninety-one percent of patients developed alopecia, 39.5% had mucositis (WHO grade 3, 9.5%) and 60.5% had some degree of emesis (11.5% nausea, 46.5% transient vomiting, 2.5% intractable vomiting). No toxic deaths occurred. CONCLUSION Chronic oral etoposide appears to be an active and well-tolerated regimen in MBC patients previously exposed to chemotherapy. This schedule of etoposide administration warrants further studies, alone or in combination, in MBC.
Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group.
Authors: Loehrer P J , Kim K , Aisner S C , Livingston R , Einhorn L H , Johnson D , Blum R 
Published: February 2017

PURPOSE The purpose of this study was to evaluate the impact of cisplatin, doxorubicin, and cyclophosphamide (PAC) in patients with advanced thymoma with respect to response rate, duration of remission, and overall survival. PATIENTS AND METHODS Assessable patients with thymoma (n = 29) or thymic carcinoma (n = 1) with metastatic or locally progressive recurrent disease following radiotherapy were treated with intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) with normal saline hydration. Courses were repeated every 3 weeks for a maximum of eight cycles of therapy. RESULTS Toxicity, which was primarily hematologic, was mild, with only one patient developing a fever associated with neutropenia. Three complete responses (CRs) and 12 partial responses (PRs) were observed (CR+PR rate, 50%; 95% confidence interval, 31.3% to 68.7%). Ten patients had stable disease. The median duration of response was 11.8 months (range, 0.9 to 70.5+), the time to treatment failure 18.4 months (range, 0.8 to 91.9+), and median survival time 37.7 months (range, 2 to 91.9+). CONCLUSION This trial demonstrates that objective response rates and prolonged survival can be achieved in patients with advanced thymoma.
High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group.
Authors: Siegert W , Beyer J , Strohscheer I , Baurmann H , Oettle H , Zingsem J , Zimmermann R , Bokemeyer C , Schmoll H J , Huhn D 
Published: February 2017

PURPOSE This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer. PATIENTS AND METHODS Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response. RESULTS The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%). CONCLUSION High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.
Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients.
Authors: Abbruzzese J L , Abbruzzese M C , Hess K R , Raber M N , Lenzi R , Frost P 
Published: February 2017

PURPOSE To evaluate the natural history, validate previous observations, and identify prognostic factors in patients with unknown primary carcinoma (UPC). PATIENTS AND METHODS Nine hundred twenty-seven consecutive patients referred to the M.D. Anderson Cancer Center with a preliminary diagnosis of UPC were prospectively identified. A standardized evaluation narrowed the study population to 657 patients with UPC. All data were recorded and computerized for storage, retrieval, and analysis. The primary end point for the study was survival, which was calculated from the first day of patient registration. Survival curves were estimated using the Kaplan-Meier method and compared using the Cox-Mantel log-rank test. To identify important prognostic factors, univariate and multivariate analyses were conducted. RESULTS The demographics of the UPC patient population mirrored those of the general population of patients referred to our cancer center except for an excess of men among the UPC patients. Most patients had histologic or cytologic evidence of adenocarcinoma and had more than one organ site metastatically involved. Univariate and multivariate analyses identified numerous important prognostic factors with a significant influence on survival, including sex, number of organ sites involved, specific organ sites involved, and pathologic subtypes. CONCLUSION This study validated previously identified important prognostic factors for survival in UPC. Additional variables that had an impact on survival were identified and the complex interaction of the factors was explored. As patient numbers increase, this database will be able to provide further analyses of patient subsets and potentially relate specific clinical features to the evolving molecular and biochemical understanding of these malignancies.
Treatment of hepatocellular carcinoma: too many options?
Authors: Venook A P 
Published: February 2017

PURPOSE This study attempts to review the therapeutic interventions being used to treat patients with hepatocellular carcinoma (HCC). DESIGN An English language literature search, including abstracts and original articles, and a review of the bibliographies of such articles, was conducted. RESULTS Surgery is possible in few patients and curative in only a small percentage. Conventional chemotherapy is ineffective in HCC. Modifications of chemotherapy, including intraarterial infusion, chemoembolization, lipiodol, styrene-maleic acid-neocarzinostatin (SMANCS), and isolated hepatic perfusion, have led to improved tumor responses, but have not materially affected patient outcome. Radioimmunotherapy and conformal radiotherapy have had no more than a marginal impact on patient outcome. Surgical innovations such as cryosurgery and percutaneous alcohol injection have not yet been shown to offer any advantage, and liver transplantation, while curative in some patients, requires an enormous expenditure of resources to achieve cure in few patients. CONCLUSION Prevention is the ideal approach to HCC. Surgical cure is rarely possible, and while numerous therapies may palliate symptoms, patient selection and the lack of randomized studies make their impact on median survival difficult to assess. Patients being treated for HCC should be enrolled on treatment protocols testing multimodality or new strategies.
Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma.
Authors: López-Guillermo A , Montserrat E , Bosch F , Terol M J , Campo E , Rozman C 
Published: February 2017

PURPOSE Variables used to build up the International Index for aggressive lymphomas (age, performance status, stage, extranodal involvement, and lactic dehydrogenase [LDH]) are also important in low-grade lymphoma. To assess the prognostic value of this index in low-grade lymphoma, we have applied it to a series of 125 patients. PATIENTS AND METHODS One hundred twenty-five patients with low-grade lymphoma who were diagnosed at a single institution over a 20-year period and treated with standard chemotherapy were studied. End points of the study were response to therapy and survival according to the International Index. In addition to the International Index, main initial and evolutive variables were evaluated. Univariate and multivariate methods were used. RESULTS After applying the International Index, the patients divided into four risk groups: low (36% of cases), low-intermediate (32%), high-intermediate (20.8%), and high (11.2%), with complete response (CR) rates in the four groups being 60%, 35%, 23%, and 21%, respectively. Ten-year overall survival rates for the risk groups were as follows: low, 73.6%; low-intermediate, 45.2%; high-intermediate, 53.5%; and high, 0% (P < .001). When the International Index was included in a multivariate analysis, along with the main initial variables, International Index (P < .001) and sex (male, worse) (P = .038) were the only parameters related to survival. When response to therapy was also included, achievement of CR (P < .0001) and International Index (P < .001) were the most important factors. In patients who achieved a CR, the International Index was the only parameter related to survival (P = .051). The results were the same when the International Index was applied to the subset of 107 patients with follicular lymphoma. CONCLUSION In this study, the International Index has been found to be an important prognostic tool in low-grade lymphomas. Such an index could be used to predict prognosis not only in aggressive, but also in low-grade lymphomas.
Primary small-intestinal lymphomas in Taiwan: immunoproliferative small-intestinal disease and nonimmunoproliferative small-intestinal disease.
Authors: Shih L Y , Liaw S J , Dunn P , Kuo T T 
Published: February 2017

PURPOSE The clinicopathologic findings in 45 adult Chinese patients with primary small-intestinal lymphoma (PSIL) are described and compared with those in Western countries and in underdeveloped nations. The efficacy of combination chemotherapy is also assessed. PATIENTS AND METHOD Six patients had immunoproliferative small-intestinal disease (IPSID) indicated by the presence of alpha-heavy chain protein (alpha-CP) in body fluids or tumor tissues. Thirty-nine patients had non-IPSID, including one with postrenal transplant lymphoma. Thirty-three non-IPSID patients received a minimum of four cycles of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). RESULTS All IPSID patients presented with the clinical and laboratory features of severe intestinal malabsorption, and all had diffuse lymphoplasmacytic infiltration in the mucosa of the small bowel. Lymphomas were localized mainly in the jejunum and mesenteric nodes. The histologic subtypes were diffuse large cell in two, immunoblastic in three, and diffuse mixed in one. All patients responded poorly to chemotherapy, with a median survival duration of 10.5 months. The common presenting symptoms of the 39 non-IPSID patients included abdominal pain (90%), weight loss (31%), abdominal mass (26%), obstruction (26%), and perforation (23%). Diffuse large-cell and immunoblastic lymphomas constituted 82% of cases. Four patients had stage IE, 19 stage II 1E, and 16 stage 112E disease according to the Musshoff's criteria; 22 had bulky tumors and 19 had multiple tumors. The tumors were completely resected in 14 patients. Of 33 patients treated with combination chemotherapy, 73% achieved a complete remission. With a median follow-up duration of 90 months, there have been four relapses, with only one at the primary tumor site. The overall 5-year survival and disease-free survival rates for non-IPSID patients who were treated with chemotherapy were 59% and 54%, respectively. CONCLUSION Intensive chemotherapy produces long-term disease-free survival in locally advanced non-IPSID PSIL.
Salvage chemotherapy in patients with extragonadal nonseminomatous germ cell tumors: the Indiana University experience.
Authors: Saxman S B , Nichols C R , Einhorn L H 
Published: February 2017

PURPOSE Patients with relapsed extragonadal germ cell tumors (EGCT) are usually treated in an identical fashion as patients with recurrent testicular cancer. However, little is known about the long-term outcome in these patients and whether they have comparable results to patients with a testicular primary tumor. The purpose of this study was to evaluate the effect of salvage chemotherapy on long-term survival in patients with EGCT. MATERIALS AND METHODS We conducted a retrospective review of 73 patients with relapsed extragonadal nonseminomatous germ cell tumors (GCTs) treated at Indiana University between 1976 and 1993. All patients received cisplatin-containing regimens as primary chemotherapy. RESULTS Only five of 73 patients (7%) were long-term disease-free survivors after salvage chemotherapy. The remaining 68 patients are either dead of disease or toxicity (n = 63), or alive with progressive disease (PD) (n = 5). Twenty-eight patients received high-dose chemotherapy with autologous bone marrow transplant (ABMT) at some point during their disease, and none of these patients are continuously disease-free. CONCLUSION Although similar salvage chemotherapy strategies will cure approximately 30% of patients with recurrent testicular cancer, new approaches are needed for EGCT.
A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study.
Authors: Thigpen J T , Blessing J A , DiSaia P J , Yordan E , Carson L F , Evers C 
Published: February 2017

PURPOSE From 1979 to 1984, 356 eligible patients with advanced or recurrent endometrial carcinoma no longer amenable to therapy with surgery, radiotherapy, or progestins were treated with doxorubicin alone or doxorubicin in combination with cyclophosphamide. PATIENTS AND METHODS Patients were randomized to receive doxorubicin 60 mg/m2 intravenously (i.v.) with or without cyclophosphamide 500 mg/m2 i.v. every 3 weeks for eight drug courses. All patients had received prior therapy with progestins with subsequent progression of disease. No patients had received prior therapy with cytotoxic drugs. Of 356 patients, 300 had measurable disease. RESULTS Among 132 patients treated with doxorubicin alone, there were seven complete responses (5%), 22 partial responses (17%), 73 with stable disease (55%), and 30 with increasing disease within 2 months of study entry (23%). For the 144 patients who received the combination, there were 18 complete responses (13%), 25 partial responses (17%), 75 with stable disease (52%), and 26 with increasing disease (18%). The median progression-free interval for those patients who received doxorubicin alone was 3.2 months, while it was 3.9 months for those who received the combination. The median survival duration for doxorubicin patients was 6.7 months, while it was 7.3 months for the combination patients. None of the unadjusted estimates of treatment differences are statistically significant. Prognostic features that had an impact on outcome included one factor associated with an increased likelihood of response (presence of measurable lung metastases) and four features associated with a poorer survival (poor performance status [PS] of 2 or 3, high pathologic grade, and presence of liver metastases or other intraabdominal disease). If these features are taken into account in multivariate analyses, there is no statistically significant evidence for differences in response rates (relative odds of response, 1.58; P = .06, one-tailed test), and survival duration is slightly longer in the combination regimen (17% reduction in death rate; P = .048). CONCLUSION The combination of doxorubicin plus cyclophosphamide thus appears to offer a small advantage over doxorubicin alone in the management of endometrial carcinoma at the expense of more frequent and severe myelosuppression and gastrointestinal toxicity.
Methotrexate pharmacokinetics and prognosis in osteosarcoma.
Authors: Graf N , Winkler K , Betlemovic M , Fuchs N , Bode U 
Published: February 2017

PURPOSE The influence of methotrexate (MTX) pharmacokinetic parameters on the efficacy of high-dose MTX (HDMTX) in osteosarcoma was analyzed. PATIENTS AND METHODS MTX serum peak values from 198 patients in 1,703 treatment courses and more detailed pharmacokinetic data from 185 patients in 1,045 treatment courses from the Cooperative Osteosarcoma Study Group (COSS) studies COSS-80, COSS-82, and COSS-86 were investigated. RESULTS A mean threshold peak level of > or = 1,000 mumol/L for the repeated MTX courses of individual patients was found to correlate significantly to prognosis in study COSS-80 (18% v 64% actuarial 10-year disease-free survival [DFS], P = .0001). Six courses of HDMTX per patient who achieved peak values > or = 1,000 mumol/L were found to be sufficient for a full effect to be seen in DFS in COSS-80. The MTX peak level was found to correlate closely to the area under the curve (AUC). However, AUC was a less powerful determinator of prognosis than the mean threshold MTX peak value. In patients who received cisplatin (DDP) as one of the additional drugs to MTX, the peak values and AUC were significantly increased (1,396 v 1,276 mumol/L, P = .011; 6,684 v 5,820 h.mumol/L, P < or = .002) and only a few patients (6%) did not achieve mean threshold MTX peak values. In addition, following restriction of hydration fluid after the MTX infusion from 4.5 to 3.0 L/m2 per 24 hours, the early MTX half-life (t1/2) and the AUC, but not the MTX peak value, were significantly increased (3.4 v 3.05 hours, and 6,760 v 5,998 h.mumol/L, respectively, P < or = .002). CONCLUSION MTX pharmacokinetics significantly influence the efficacy of MTX in osteosarcoma. Individual adaptation of the MTX dose to ensure a threshold peak serum level > or = 1,000 mumol/L does not seem necessary at a fixed dose of 12 g MTX/m2, restriction of hydration fluid to 3 L/m2 per 24 hours, and concomitant use of DDP within the drug regimen.
Phase I study of docetaxel administered as a 1-hour intravenous infusion on a weekly basis.
Authors: Tomiak E , Piccart M J , Kerger J , Lips S , Awada A , de Valeriola D , Ravoet C , Lossignol D , Sculier J P , Auzannet V 
Published: February 2017

PURPOSE This phase I study of Taxotere (RP 56976, NSC 628503; docetaxel, Rhône-Poulenc Rorer, Antony, France) was undertaken to determine the maximum-tolerated dose (MTD), toxic effects, and basic pharmacokinetics of a day-1 and -8 schedule of this novel semisynthetic product related to Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT). PATIENTS AND METHODS Thirty-two eligible patients with refractory solid malignancies have been treated with a 1-hour infusion of Taxotere on a day-1 and -8 schedule every 3 weeks as long as patients maintained a polymorphonucleotide count > or = 1,500/microL and a platelet count > or = 100,000/microL. Dose levels tested have ranged between 20 and 110 mg/m2 per course. RESULTS Considering 128 assessable courses, the main toxicities have been neutropenia (which was dose-limiting), asthenia, alopecia, hypersensitivity reactions, skin toxicity, and edema. No significant cardiac or platelet toxicity has been observed. Seven patients have had aggravation of preexisting paresthesias or new onset of sensory symptoms during Taxotere treatment. The MTD at this schedule appears to be 110 mg/m2 per course, with six of 10 patients at this level experiencing severe toxicity. Five partial remissions have been observed in four heavily pretreated patients with breast cancer and in one patient with adenocarcinoma of unknown origin. Two patients with ovarian cancer have had meaningful decreases in CA125 levels. CONCLUSION Like Taxol, this novel chemotherapeutic agent appears to possess promising activity in patients with refractory breast and ovarian neoplasms, with tolerable toxicities. Using this schedule, 100 mg/m2 per course is the recommended dose for future phase II trials.