bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors.
Authors: Marina N M , Rodman J , Shema S J , Bowman L C , Douglass E , Furman W , Santana V M , Hudson M , Wilimas J , Meyer W 
Published: February 2017

PURPOSE The tolerance of escalating targeted doses of carboplatin combined with ifosfamide (IFOS)/etoposide (VP-16) (ICE) was assessed in children with recurrent solid tumors. PATIENTS AND METHODS To reduce interpatient variability in carboplatin systemic exposure, 45 children were treated with doses individualized to a target area under the serum concentration versus time curve (AUC) based on renal function, using technetium 99-diethyl-enetriamine pentaacetic acid (99mTc-DTPA) clearance to estimate glomerular filtration rate (GFR). Cohorts of at least three patients received carboplatin at an initial target AUC of 2 mg/mL x min, with escalations of 1 mg/mL x min in subsequent cohorts. Courses consisted of carboplatin on day 1 followed by IFOS 2 g/m2 plus VP-16 100 mg/m2 on days 2 and 3. Patients received at least two courses, with a maximum of eight courses possible in the absence of progressive disease. When only moderate toxicity occurred after escalation to 5 mg/mL x min, a third dose of IFOS plus VP-16 was added. After three patients were treated at this level, carboplatin escalation proceeded. RESULTS Neutropenia and thrombocytopenia were the dominant toxicities in the 43 assessable patients. At the target AUC of 8 mg/mL x min, 13 of 20 cycles were associated with febrile neutropenia. For phase II trials, we recommend a carboplatin target AUC of 6 mg/mL x min with three doses of IFOS and VP-16 for patients with prior craniospinal irradiation or high-dose cisplatin (CDDP)/VP-16, or 7 mg/mL x min for patients without such histories. There were two complete responses (CRs), 13 partial responses (PRs), and 17 objective responses (ORs). CONCLUSION The ICE regimen shows promising activity in pediatric solid tumors. The clear relationship between hematologic toxicity and carboplatin systemic exposure supports the use of targeted dosing in further trials of ICE chemotherapy.
Escalating dose of continuous infusion combination chemotherapy for refractory neuroblastoma.
Authors: Campbell L A , Seeger R C , Harris R E , Villablanca J G , Matthay K K 
Published: February 2017

PURPOSE This trial was undertaken to determine if a continuous infusion format with increased dose-intensity had antitumor activity with tolerable toxicity in patients with advanced neuroblastoma. PATIENTS AND METHODS Forty heavily pretreated patients with refractory or progressive neuroblastoma received continuous infusion doxorubicin, cisplatin, and etoposide along with bolus ifosfamide in a dose-escalation format. A total of 79 courses of chemotherapy were administered at five different dose levels. RESULTS Fifteen of 35 assessable patients (43%) achieved either a partial response (PR) or complete response (CR), including five patients with a CR, three with a very good PR (VGPR), and seven with a PR. Hematologic toxicity was severe, but reversible, and other toxicities, although significant, were tolerable and much less than that accepted in a bone marrow transplantation (BMT) setting. CONCLUSION This investigation illustrates that response is possible even in an extremely poor-prognosis group of patients, and it suggests that such a regimen may be effective if given before disease progression occurs.
Phase I and plasma pharmacokinetic study of infusional fluorouracil combined with recombinant interferon alfa-2b in patients with advanced cancer.
Authors: Danhauser L L , Freimann J H , Gilchrist T L , Gutterman J U , Hunter C Y , Yeomans A C , Markowitz A B 
Published: February 2017

PURPOSE Enhanced fluorouracil (FUra) cytotoxicity caused by recombinant interferon alfa-2b (rIFN-a) has been reported, but the mechanism, optimal dose, and schedule remain unknown. Therefore, a phase I and pharmacokinetic study of FUra with escalating doses of rIFN-a was initiated. PATIENTS AND METHODS FUra (750 mg/m2/d) was given by continuous intravenous (IV) infusion for 5 days. rIFN-a (0.1 to 15 x 10(6) U/m2/d) was given subcutaneously (SC) daily for 5 days concurrent with FUra. Courses were repeated every 14 to 21 days. Forty-four patients were enrolled; 39 received at least two courses. During the first course of therapy, FUra levels before and after administration of rIFN-a were quantitated in 26 patients by high-pressure liquid chromatography. RESULTS The maximum-tolerated dose of rIFN-a was 10 x 10(6) U/m2/d. Stomatitis was dose-limiting. Three partial and five minor responses occurred. Interpatient pharmacokinetics showed that rIFN-a did not alter steady-state plasma concentration (Css; range, 0.77 +/- 0.35 mumol/L to 1.85 +/- 0.48 mumol/L), elimination half-life (t1/2; mean, 9.7 +/- 4.3 minutes), area under the concentration-versus-time curve (AUC; range, 93 to 224 mumol/L x hours), total-body clearance (CI; range, 1,172 to 3,236 mL/min), or volume of distribution (range, 11.9 to 49.2 L) of FUra. Intrapatient data evaluation revealed a dose-independent effect of rIFN-a. The mean FUra Css after rIFN-a administration (1.31 mumol/L) was greater than that before rIFN-a administration (1.02 mumol/L, P < .0001). FUra Cl after rIFN-a administration was reduced by 20% to 35% compared with use of FUra alone (P < .0001). Patients with a greater than 20% decrease in FUra Cl had a fourfold greater incidence of diarrhea. CONCLUSION rIFN-a reduces FUra Cl and, consequently, increases FUra-associated toxicity. Phase II studies of FUra and rIFN-a seem to be warranted.
Characteristics of women at risk for psychosocial distress in the year after breast cancer.
Authors: Schag C A , Ganz P A , Polinsky M L , Fred C , Hirji K , Petersen L 
Published: February 2017

PURPOSE To provide a detailed description of rehabilitation problems of women, considered to be low risk and at risk for psychosocial morbidity, diagnosed with stage I and II breast cancer 1 month and 1 year after primary treatment. PATIENTS AND METHODS A sample of 227 newly diagnosed breast cancer patients were systematically interviewed by a clinical social worker and classified for risk of psychosocial distress in the year after diagnosis. They completed a battery of standardized instruments to assess quality of life (QL), rehabilitation needs, and psychologic distress. The primary QL instrument, the Cancer Rehabilitation Evaluation System (CARES), provides a detailed listing of rehabilitation needs. Descriptive CARES data are presented with comparisons between the two groups. RESULTS The at-risk women had significantly more problems with greater severity than the low-risk women in all areas (physical, psychosocial, medical interaction, sexual, and marital). While both groups showed improvement over the year following diagnosis, the at-risk group had significantly more problems 1 year later. Many physical problems subside, but problems at the local surgical site, psychologic distress, communication with marital partners, and negative body image are more persistent in the at-risk group 1 year later, while half of both groups continue to have sexual dysfunction. CONCLUSION The detailed listing of problems provided by the CARES may be helpful to clinicians in their interactions with patients. The need for preventive and early intervention for the at-risk patients is underscored.
Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia.
Authors: Wolfrom C , Hartmann R , Fengler R , Brühmüller S , Ingwersen A , Henze G 
Published: February 2017

PURPOSE Pharmacokinetics, toxicity, and therapeutic efficacy of two different methotrexate (MTX) infusions for remission induction of relapsed childhood acute lymphoblastic leukemia (ALL) were investigated in a randomized multicenter trial. PATIENTS AND METHODS Sixty patients with early bone marrow relapse received a polychemotherapy induction protocol starting with either 12 g/m2 MTX as a 4-hour infusion (high-dose [HDM]) or 1 g/m2 as a 36-hour infusion (intermediate-dose [IDM]). In HDM, leucovorin (LCV) was administered orally (12 times, 15 mg/m2 every 6 hours), beginning at hour 24. In IDM, only two doses were administered at hours 48 and 54. RESULTS Median serum MTX concentrations during infusion were 716 mumol/L in HDM and 7.2 mumol/L in IDM. In HDM, MTX serum levels at hour 24 (median, 2.8 mumol/L) were significantly less than steady-state levels of IDM. Concentrations greater than 1 mumol/L were maintained for 36 hours with HDM and 45 hours with IDM. General tolerance to treatment was better in the HDM group. Mucosal lesions occurred significantly more often and were more severe after IDM treatment. A median treatment delay of 3 days was required in the IDM group but not in the HDM group. At day 15, complete remission (CR) was documented in 45% of IDM- and 48% of HDM-treated patients. Persistent blasts (> 5%) appeared more frequently in HDM than in IDM (35% v 19% of patients; P = NS). After completion of induction therapy, 28 of 30 patients in each group achieved CR. CONCLUSION Both regimens produced the same remission rates. The tendency to better antileukemic activity of IDM was accompanied by more severe side effects as a consequence of long-lasting cytotoxic MTX levels. Hence, long-term infusion of IDM followed by low-dose LCV is an effective treatment for recurrent ALL.
Unrelated-donor bone marrow transplantation for Philadelphia chromosome-positive chronic myelogenous leukemia in children.
Authors: Gamis A S , Haake R , McGlave P , Ramsay N K 
Published: February 2017

PURPOSE Bone marrow transplantation (BMT) for Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML) results in a 55% to 64% disease-free survival (DFS) rate in 20% to 30% of cases with a matched-sibling donor (MSD). Studies that include primarily adults with CML, using unrelated-donor (URD) BMT, have expanded this option to those without an MSD. We review and compare the efficacy of URD and MSD BMT in children with Ph1 CML. PATIENTS AND METHODS Eleven children with URD BMTs were reviewed and compared with 11 children with MSD BMTs for Ph1 CML. Among the URD BMT recipients, there were three with fully matched marrows and 10 with advanced CML. The median time from diagnosis to transplant was 2.6 years. Among the MSD BMT recipients, 11 had fully matched marrows and five had advanced CML. The median time from diagnosis to BMT was 0.7 years. All received non-T-depleted marrows after cyclophosphamide and fractionated total-body irradiation. RESULTS Both groups had similar engraftment times. Late graft failure occurred in two URD patients. Graft-versus-host disease (GVHD), > or = grade II, was similar in both groups (77% for URD BMT, 45% for MSD BMT), although more severe acute disease and more persistent chronic disease was seen in the URD group. The Kaplan-Meier estimate of DFS was 45% +/- 15% (SE) and 78% +/- 14% (SE) in the URD and MSD groups, respectively, at 3 years. All had Karnofsky scores of more than 70%, except one URD patient debilitated from GVHD. CONCLUSION CML is eventually fatal to all patients without BMT. The high survival rate seen among children who receive a URD BMT, despite several adverse factors, opens this important therapeutic option to those without an MSD.
Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study.
Authors: Pullen J , Boyett J , Shuster J , Crist W , Land V , Frankel L , Iyer R , Backstrom L , van Eys J , Harris M 
Published: February 2017

PURPOSE The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis. PATIENTS AND METHODS With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype. RESULTS The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome. CONCLUSION TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.
Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood.
Authors: Packer R J , Lange B , Ater J , Nicholson H S , Allen J , Walker R , Prados M , Jakacki R , Reaman G , Needles M N 
Published: February 2017

PURPOSE This study investigates the response rate to and toxicity of carboplatin and vincristine in children with recurrent low-grade gliomas (LGGs) or patients younger than 60 months with newly diagnosed LGGs. PATIENTS AND METHODS Twenty-three children with recurrent and 37 children with newly diagnosed LGGs were treated with a 10-week induction cycle of carboplatin and vincristine, followed by maintenance treatment with the same drugs. Patients were evaluated for response to treatment and toxicity. RESULTS Twelve of 23 (52% +/- 10%; 95% confidence interval [CI], 0.32 to 0.72) assessable children with recurrent disease had an objective response to treatment, which included a greater than 50% reduction in tumor size in seven of 23 (30% +/- 10%; 95% CI, 0.10 to 0.50). Twenty-three of 37 (62% +/- .08; 95% CI, 0.46 to 0.78) of newly diagnosed patients had an objective response, 16 of 37 (43% +/- 0.08%; 95% CI, 0.27 to 0.59) with greater than 50% reduction in tumor size. The majority of those with an objective response had diencephalic tumors (n = 29), but children with thalamic (n = 2), cortical (n = 1), and brain stem (n = 2) LGGs also responded to treatment. Of the 35 patients with objective response to treatment, the maximum response was seen in 25 after completion of induction and in the remaining 10 after two to six cycles of maintenance treatment. Forty-nine of 53 (92% +/- .04%) patients who were stable or improved after induction remain without progressive disease (PD). Hematologic toxicity was common, but resulted in cessation of therapy in only one patient. Six children have been removed from the study because of allergic reactions, which were considered to be carboplatin-associated. CONCLUSION Carboplatin and vincristine have activity in children with recurrent and newly diagnosed progressive LGGs. Objective responses to treatment after chemotherapy can be seen. This drug regimen is relatively well tolerated, and further studies are indicated to define the role of this combination of drugs in children with newly diagnosed LGGs.
Alternating chemotherapy and twice-daily thoracic radiotherapy in limited-stage small-cell lung cancer: a pilot study of the Eastern Cooperative Oncology Group.
Authors: Johnson D H , Turrisi A T , Chang A Y , Blum R , Bonomi P , Ettinger D , Wagner H 
Published: February 2017

PURPOSE This pilot study was undertaken to determine the efficacy and feasibility of alternating cisplatin and etoposide with multiple daily fractions of thoracic radiotherapy (TRT) in patients with limited-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS Thirty-four SCLC patients received four courses of cisplatin (30 mg/m2/d x 3) plus etoposide (120 mg/m2/d x 3) (PE) every 3 weeks. TRT was administered twice daily (1.5 Gy per fraction) for 5 consecutive days in the week after cycles 1, 2, and 3 of chemotherapy (total TRT dose, 45 Gy). Patients who achieved a complete response (CR) received one course of late-intensification (LI) treatment consisting of cyclophosphamide (4 g/m2) and etoposide (900 mg/m2). Prophylactic cranial irradiation (PCI) was optional. RESULTS Nineteen of 32 assessable patients achieved a CR (59%) and 12 had a partial response (38%), for an overall response rate of 97% (95% confidence interval [CI], 84% to 99%). Median survival was 18 months, while 2-year progression-free survival was 47%. Leukopenia < or = 1,000/microL occurred in 12% of induction treatment cycles. Severe esophagitis was uncommon. Pulmonary fibrosis that was asymptomatic or minimally symptomatic was observed in eight patients (25%). There was one episode of adult respiratory distress syndrome (ARDS) during LI chemotherapy. Life-threatening neutropenia (< or = 500/microL) developed in all patients who underwent LI chemotherapy, with a median duration of 10 days (range, 8 to 19). Two patients died of sepsis during LI chemotherapy. CONCLUSION Alternating PE and TRT as performed in this trial is an effective brief induction regimen for limited-stage SCLC. However, this particular regimen did not appear to be substantially different in terms of efficacy or toxicity compared with regimens using concurrent chemotherapy and standard-fraction TRT. LI chemotherapy was associated with unacceptable toxicity and did not appear to have a favorable impact on survival.
Prognostic value of PS2 and cathepsin D in 710 human primary breast tumors: multivariate analysis.
Authors: Foekens J A , van Putten W L , Portengen H , de Koning H Y , Thirion B , Alexieva-Figusch J , Klijn J G 
Published: February 2017

PURPOSE Evaluation of the prognostic value of cytosolic PS2 (pS2 protein) and cathepsin D in a large series of breast cancer patients by multivariate analysis taking into account steroid receptors and conventional prognostic factors. PATIENTS AND METHODS Prognostic factors were analyzed in 710 primary breast cancers (median follow-up, 4 years). PS2 and cathepsin D were measured by radiometric immunoassays. Estrogen receptor (ER) and progesterone receptor (PgR) status were assessed by radioligand binding assays and multiple-point Scatchard analysis. RESULTS The best cutoff point for PS2 to discriminate between positive (61% of the tumors) and negative was 2 ng/mg protein (univariate P value in 5-year relapse-free survival = .003). For cathepsin D, no sensible cutoff point could be chosen, since there was a continuous association between the level of cathepsin D and relapse rate (P = .001). In Cox multivariate analysis, relapse rate decreased with age of premenopausal/perimenopausal patients and with PS2 or steroid receptor positivity, and increased with the size of the tumor, the number of positive lymph nodes, and increasing levels of cathepsin D. In analysis for overall survival, age of both premenopausal/perimenopausal and postmenopausal patients, tumor size, the number of positive lymph nodes, ER/PgR, and PS2 were all independently associated with the rate of death. The level of cathepsin D was positively correlated with the rate of death, but this trend was not statistically significant. Separate Cox multivariate analyses for relapse-free survival in subgroups of patients as defined by nodal status showed that the contribution of PS2 and cathepsin D was the strongest in the node-negative subgroup. Node-negative patients with tumors containing PS2 values < or = 2 ng/mg protein and cathepsin D values more than 70 pmol/mg protein experienced a 4.5-fold increase in relapse rate as compared with those with PS2 levels greater than 2 ng/mg protein and cathepsin D levels < or = 30 pmol/mg protein. CONCLUSION PS2 and cathepsin D are independent prognostic factors in primary breast cancer and lymph node-negative patients.
Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group.
Authors: Shimada Y , Yoshino M , Wakui A , Nakao I , Futatsuki K , Sakata Y , Kambe M , Taguchi T , Ogawa N 
Published: February 2017

PURPOSE A phase II study was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with metastatic colorectal cancer. PATIENTS AND METHODS From December 1989 to March 1991, 67 patients with metastatic colorectal cancer were enrolled in this study. Sixty-three patients were assessable for toxicity and response. Their median age was 57 years (range, 24 to 72). Forty-six patients (73%) had a good performance status of 0 or 1. Fifty-one patients (81%) had received prior chemotherapy. The major sites of metastasis were liver (63%) and lung (44%). CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion, or as 150 mg/m2 every 2 weeks. The dose was reduced based on the grade of leukopenia and diarrhea, if necessary. RESULTS A partial response was obtained in 17 of 63 assessable patients (27%; 95% confidence interval, 16% to 38%). The response rate in patients with prior radiotherapy or chemotherapy was 25% (13 of 52). Liver metastases showed a 15% (six of 40) response and lung metastases showed a 39% (11 of 28) response. The median duration of partial response was 127 days (range, 49 to 353) and the median overall duration of response was 208 days (range, 99 to 381). The major toxicities (> or = grade 3) were leukopenia (16%), diarrhea (13%), nausea and vomiting (13%), and alopecia (11%). Adverse effects were generally well tolerated and reversible. Treatment could be continued on an outpatient basis for patients without severe toxicity. Hemorrhagic cystitis was not encountered in this study. CONCLUSION CPT-11 showed promising antitumor activity against metastatic colorectal cancer that was resistant to prior therapy. Further clinical trials of combination chemotherapy using CPT-11 are justified.