bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose paclitaxel, cyclophosphamide, and cisplatin with autologous hematopoietic progenitor-cell support: a phase I trial.
Authors: Stemmer S M , Cagnoni P J , Shpall E J , Bearman S I , Matthes S , Dufton C , Day T , Taffs S , Hami L , Martinez C , Purdy M H , Arron J , Jones R B 
Published: February 2017

PURPOSE To determine the maximal-tolerated dose (MTD) of paclitaxel in combination with high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous hematopoietic progenitor-cell support (AHPCS). PATIENTS AND METHODS Forty-nine patients with poor-prognosis breast cancer, non-Hodgkin's lymphoma (NHL), or ovarian cancer were treated with escalating doses of paclitaxel infused over 24 hours, followed by CPA (5,625 mg/m2 intravenously over 1 hour in three divided doses) and cDDP (165 mg/m2 intravenously as a continuous infusion over 72 hours) and AHPCS. Pharmacokinetic measurements for each drug were performed. RESULTS Dose-limiting toxicities were encountered in two patients at 825 mg/m2 of paclitaxel; one patient died of multiorgan failure that involved the lung, CNS, and kidneys, and the other developed grade 3 respiratory, CNS, and renal toxicity, which resolved. The MTD of this combination was determined to be paclitaxel 775 mg/m2, CPA 5,625 mg/m2, and cDDP 165 mg/m2 followed by AHPCS. Sensory polyneuropathy and mucositis were prominent toxicities, but both were reversible and tolerable. The pharmacokinetics of paclitaxel correlated significantly with the severity of mucositis (P < .001) and peripheral neuropathy (P < .00004). Eighteen of 33 patients (54%) with measurable, heavily pretreated metastatic breast cancer achieved a partial response (PR). Responses were also observed in patients with NHL (four of five patients) and ovarian cancer (two of two). CONCLUSION It is possible to escalate the dose of paclitaxel to 775 mg/m2 in combination with 5,625 mg/m2 of CPA, 165 mg/m2 of cDDP, and AHPCS. An encouraging response rate in poor-prognosis patients with breast cancer, NHL, and ovarian cancer warrants further study.
Feasibility of multiple courses of high-dose cyclophosphamide, thiotepa, and carboplatin for breast cancer or germ cell cancer.
Authors: Rodenhuis S , Westermann A , Holtkamp M J , Nooijen W J , Baars J W , van der Wall E , Slaper-Cortenbach I C , Schornagel J H 
Published: February 2017

PURPOSE To determine the feasibility and safety of multiple, closely timed courses of high-dose cyclophosphamide, thiotepa, and carboplatin (CTC) with peripheral-blood progenitor-cell transplantation (PBPCT). PATIENTS AND METHODS Forty-eight patients with advanced cancer were scheduled to undergo either two or three courses of CTC with PBPCT. All PBPCs were harvested before high-dose therapy began. Full-dose CTC courses incorporated cyclophosphamide (6,000 mg/m2), thiotepa (480 mg/m2), and carboplatin (1,600 mg/m2) divided over days -6, -5, -4, and -3. Tiny CTC courses (tCTC) contained 67% of the doses of each of these agents. Second or third courses of CTC or tCTC began on day 28. RESULTS A sufficient number of PBPC could be harvested from all but two patients. Thirty-five first full-dose courses of CTC were given, 28 second courses, and 10 third courses. Second courses could be given on time and at full dose in 80% of the patients, but there was one toxic death from venoocclusive disease (VOD). Only four of 12 patients scheduled to receive three courses of full-dose CTC could be treated at the time and dose planned. There were three toxic deaths: one of VOD, one of sepsis, and one of hemolytic uremic syndrome (HUS). Eight patients were scheduled to receive three courses of tCTC. Eight first, seven second, and six third courses were given. One of the third courses had to be delayed and one had to be reduced in dose. CONCLUSION A sufficient number of PBPCs for two or three transplantations can be harvested from most patients without much difficulty before high-dose therapy. Two full-dose CTC courses or three tCTC courses can be given safely and with acceptable toxicity at 5-week intervals. Organ toxicity rather than bone marrow toxicity has become dose-limiting for alkylating agents.
Therapy of refractory or recurrent childhood acute myeloid leukemia using amsacrine and etoposide with or without azacitidine: a Pediatric Oncology Group randomized phase II study.
Authors: Steuber C P , Krischer J , Holbrook T , Camitta B , Land V , Sexauer C , Mahoney D , Weinstein H 
Published: February 2017

PURPOSE A randomized study compared the combination of amsacrine (100 mg/m2/d on days 1 to 5) and etoposide (200 mg/m2/d on days 1 to 3) with the same two agents plus azacitidine (250 mg/m2/d on days 4 to 50) for the therapy of induction-resistant or relapse childhood acute myeloid leukemia (AML). PATIENTS AND METHODS One hundred sixty-seven assessable children with AML who either had failed to respond to primary induction therapy (group 1, n = 41) or had relapsed (group 2, n = 126) were randomized. RESULTS Overall, there were 56 complete responses (34%; SE 4%). Among primary refractory patients (group 1), the complete response rate was higher with the three-drug regimen (18% vs 53%, P = .03). In the relapsed patients (group 2), there was no difference in complete response rates related to treatment (31% vs 35%, P = .3). There were 17 early deaths. The major toxicities for both regimens were myelosuppression and infection. CONCLUSION The overall complete response rate of 34% in this patient population is indicative of effective antileukemic activity. For patients with relapsed leukemia, the addition of azacitidine to etoposide and amsacrine did not improve response. The suggested advantage of the three-drug regimen for induction failures warrants further investigation.
Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma.
Authors: Kudelka A P , Tresukosol D , Edwards C L , Freedman R S , Levenback C , Chantarawiroj P , Gonzalez de Leon C , Kim E E , Madden T , Wallin B , Hord M , Verschraegen C , Raber M , Kavanagh J J 
Published: February 2017

PURPOSE To determine the efficacy and toxicity of topotecan administered as a 5-day intravenous infusion in patients with advanced ovarian cancer refractory to cisplatin-based chemotherapy. PATIENTS AND METHODS Thirty patients with advanced epithelial ovarian cancer refractory to cisplatin-based chemotherapy received intravenous infusions of topotecan 1.5 mg/m2 delivered over 30 minutes each day for 5 days. A course was repeated every 21 days. The patient eligibility requirements included age > or = 18 years, Zubrod score < or = 2, measurable disease, adequate hepatic and renal function, neutrophil count > or = 1,500/microL, platelet count > or = 100,000/microL, and anticipated survival > or = 3 months. RESULTS Twenty eight patients were assessable for response and toxicity. All patients were assessable for survival. The major toxicity from administration of topotecan at this dose schedule was myelosuppression; 21 patients required dose reductions. Four patients had neutropenic fever that required hospitalization, and seven patients required platelet transfusions. Maculopapular pruritic exanthema occurred in 20% of patients; gastrointestinal side effects were mild. No deaths were reported on the study. At dose levels of 1.5, 1.25, and 1.0 mg/m2, 61%, 31%, and 25% of patients, respectively, required dose reductions. Of 28 assessable patients, four (14%; 95% confidence interval [CI], 4% to 34%) achieved a partial response (PR) at a median of 1.4 months and lasting 8.9 months, and 17 had stable disease (SD). The overall median survival time was 10.0 months (95% CI, 8.1 to 13.5). CONCLUSION Topotecan shows modest clinical activity against cisplatin-refractory ovarian cancer, although the dose-intensity is compromised by the depth of the granulocyte nadir and the duration of granulocytopenia. Further studies of topotecan may necessitate a reevaluation of optimal dose schedule, with the possible incorporation of multilineage cytokines, and its activity in taxane-resistant tumors.
Five-day course of granulocyte colony-stimulating factor in patients with prolonged neutropenia after adjuvant chemotherapy for breast cancer is a safe and cost-effective schedule to maintain dose-intensity.
Authors: Ribas A , Albanell J , Bellmunt J , Solé-Calvo L A , Bermejo B , Gallardo E , Vidal R , Vera R , Eres N , Carulla J , Baselga J 
Published: February 2017

PURPOSE To analyze the safety and efficacy of a short course of granulocyte colony-stimulating factor (G-CSF) to maintain dose-intensity of subsequent cycles of chemotherapy after a prior episode of prolonged neutropenia, without febrile complications, in patients receiving adjuvant treatment for breast cancer. PATIENTS AND METHODS Thirty-two patients undergoing adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin-CMF for stages I to II breast cancer were included after having chemotherapy delays due to neutropenia (absolute neutrophil count [ANC] < 1.5 x 10(9)/L) on day 22. G-CSF was administered subcutaneously on days 15 to 19 of each subsequent cycle. RESULTS None of the patients included in this study had to be admitted to the hospital for fever and neutropenia. The median percentage of the projected dose-intensity for CMF or doxorubicin-CMF on an intent-to-treat basis was 0.994, which was significantly higher than the delivered dose-intensity before the start of G-CSF treatment (P < .0001). Patients who received concomitant G-CSF and radiotherapy achieved a similar dose-intensity as patients who did not undergo radiotherapy. Seven patients discontinued G-CSF treatment due to musculoskeletal pain. These patients had more subsequent cycle delays because of day 22 neutropenia than the 25 patients who followed the G-CSF schedule (P = .0028). CONCLUSION A 5-day course of G-CSF in patients with prior chemotherapy delays due to prolonged neutropenia seems to be a safe and cost-effective schedule to maintain CMF or doxorubicin-CMF dose-intensity in the adjuvant treatment of breast cancer.
Paclitaxel with mitoxantrone, fluorouracil, and high-dose leucovorin in the treatment of metastatic breast cancer: a phase II trial.
Authors: Hainsworth J D , Jones S E , Mennel R G , Blum J L , Greco F A 
Published: February 2017

PURPOSE Paclitaxel is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. In this phase II study, we added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin (NFL). PATIENTS AND METHODS Forty-six patients with metastatic breast cancer received the following regimen as first- or second-line treatment: paclitaxel 135 mg/m2 by 1-hour intravenous (i.v.) infusion on day 1, mitoxantrone 10 mg/m2 by i.v. bolus on day 1, 5-FU 350 mg2/m by i.v. bolus on days 1, 2, and 3, and leucovorin 300 mg i.v. over 30 to 60 minutes immediately preceding 5-FU on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients. RESULTS Twenty-three of 45 assessable patients (51%) had major responses. Previous chemotherapy, and in particular previous treatment with doxorubicin, did not affect response rate. The median response duration was 7.5 months. Myelosuppression was moderately severe, with 76% of courses resulting in grade 3 or 4 leukopenia. Hospitalization for treatment of fever during neutropenia was required in 13% of courses, and two patients died as a result of sepsis. Two patients developed severe congestive heart failure after a large cumulative anthracycline dose. CONCLUSION This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although its activity compared with other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than anticipated based on previous results with the NFL regimen or with paclitaxel administered at this dose and schedule as a single agent. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with the paclitaxel/doxorubicin combination.
Positron emission tomography evaluation of residual radiographic abnormalities in postchemotherapy germ cell tumor patients.
Authors: Stephens A W , Gonin R , Hutchins G D , Einhorn L H 
Published: February 2017

PURPOSE This study was performed to assess the ability of positron emission tomography (PET) to differentiate residual radiographic abnormalities in postchemotherapy nonseminomatous germ cell tumor (GCT) patients. MATERIALS AND METHODS Thirty patients with nonseminomatous GCT were evaluated with PET scans before surgical resection of a residual mass or masses. Standardized uptake values (SUV) were calculated for the region of maximal 2-fluoro-2-deoxyglucose (FDG) uptake and compared with histologic findings. RESULTS Eleven patients had necrosis/fibrosis in the resected specimen, 15 had teratoma, and four viable GCT. The median SUV for the necrosis/fibrosis group was 2.86, teratoma 3.07, and viable GCT 8.81. A significant association between SUV and histology was found when comparing viable GCT versus necrosis/fibrosis plus teratoma (P = .004). Patients with an SUV greater than 5 were 75 times more likely to have viable cancer than teratoma or necrosis/fibrosis (odds ratio; 95% confidence interval, 3.66 to 1,536). PET did not differentiate necrosis/fibrosis from teratoma. However, PET was able to differentiate viable GCT from residual necrosis/fibrosis or teratoma. CONCLUSION PET-FDG imaging can be useful for detection of residual viable carcinoma following chemotherapy in nonseminomatous GCT patients with residual masses. It may be a valuable adjunct in the determination of which patients should undergo postchemotherapy resection.
Carboplatin and paclitaxel in ovarian carcinoma: a phase I study of the Gynecologic Oncology Group.
Authors: Bookman M A , McGuire W P , Kilpatrick D , Keenan E , Hogan W M , Johnson S W , O'Dwyer P , Rowinsky E , Gallion H H , Ozols R F 
Published: February 2017

PURPOSE To develop a tolerable, dose-intense regimen of carboplatin and paclitaxel for the treatment of primary epithelial ovarian carcinoma. PATIENTS AND METHODS Patients underwent initial surgical assessment and tumor debulking. Patients with stage III/IV disease received six cycles of chemotherapy on a planned 21-day cycle. Carboplatin dose was calculated based on projected area under the curve (AUC) for concentration over time (mg. mL-1.min) and escalated to determine the maximum-tolerated dose (MTD). Paclitaxel dose was also escalated as a 3-, 24-, or 96-hour infusion. Granulocyte colony-stimulating factors (G-CSFs) were required at selected dose levels or could be added based on hematologic toxicity. RESULTS Thirty-nine patients were enrolled and assessable for toxicity and response. Dose-limiting toxicity (DLT) was hematologic, primarily neutropenia. Less than 2% of all cycles with paclitaxel as a 3- or 24-hour infusion were associated with either grade 4 thrombocytopenia or febrile neutropenia. The carboplatin MTD was AUC 7.5 (equivalent to a median dose of 471 mg/m2). The MTD for paclitaxel was 135 mg/m2 over 24 hours and 175 mg/m2 over 3 hours without initial G-CSF. A 96-hour infusion of paclitaxel at a dose of 120 mg/m2 was associated with excessive single-cycle and cumulative myelosuppression, and was not further evaluated. Measured carboplatin AUC agreed well with the calculated AUC. The overall complete (n = 16) and partial (n = 2) response rate among 24 patients with measurable disease was 75%, with a median progression-free survival time of 15 months. CONCLUSION Carboplatin could be safely combined with paclitaxel using a dose formula based on projected renal clearance. The recommended outpatient regimen is carboplatin AUC 7.5 and paclitaxel 175 mg/m2 over 3 hours without initial G-CSF. This treatment safely achieved a greater dose-intensity of carboplatin than would have been achieved with conventional dosing based on body-surface area.
Therapeutic monitoring of continuous infusion etoposide in small-cell lung cancer.
Authors: Joel S P , Ellis P , O'Byrne K , Papamichael D , Hall M , Penson R , Nicholls S , O'Donnell C , Constantinou A , Woodhull J , Nicholson M , Smith I , Talbot D , Slevin M 
Published: February 2017

PURPOSE To investigate the feasibility of therapeutic monitoring of etoposide at different plasma concentrations of the drug, and the resulting pharmacodynamic effects of such an approach. PATIENTS AND METHODS Forty-nine previously untreated small-cell lung cancer (SCLC) patients received single-agent etoposide every 3 weeks by continuous infusion over 5 days. Plasma etoposide concentrations were monitored 18 and 66 hours into the infusion to permit dose modification. The first cohort of 15 patients began treatment with etoposide 2 micrograms/mL, with dose escalation to 3 micrograms/mL for cycles 3 and 4 and 4 micrograms/mL for cycles 5 and 6, toxicity permitting. The second cohort of 34 patients commenced at 3 micrograms/mL, with dose escalation to 4 and 5 micrograms/mL on cycles 3 and 5, respectively. RESULTS Mean plasma etoposide concentration during the first treatment cycle was 93.4% +/- 26.6% of the target level at 18 hours (57% of patients within +/- 20% of the target) and 98.9% +/- 14.5% of the target level at 66 hours (82% of patients within +/- 20%). Hematologic toxicity was more pronounced in those treated with 3 micrograms/mL versus 2 micrograms/mL (median nadir neutrophil count, 1.3 v 2.6 x 10(9)/L, P = .032). Tumor responses, typically documented by the third cycle, were similar in each cohort (71% in patients commenced at 2 micrograms/mL and 70% at 3 micrograms/mL). Treatment cohort was not independently predictive of survival. CONCLUSION Therapeutic monitoring of infusional etoposide is feasible and dramatically reduces interpatient pharmacokinetic variability. Although this was a small nonrandomized trial, the observation of different hematologic toxicity at the two starting concentrations but similar antitumor activity further suggests that these effects may be associated with different plasma etoposide concentrations.
Response of recurrent medulloblastoma to low-dose oral etoposide.
Authors: Ashley D M , Meier L , Kerby T , Zalduondo F M , Friedman H S , Gajjar A , Kun L , Duffner P K , Smith S , Longee D 
Published: February 2017

PURPOSE The outcome for patients with recurrent medulloblastoma has historically been poor, with most patients dying of disseminated disease. Here, we report on seven patients with recurrent medulloblastoma, most heavily pretreated with a variety of chemotherapeutic agents, including parenteral etoposide (VP-16), who showed responses to the administration of repeated courses of low-dose oral VP-16. PATIENTS AND METHODS Seven patients age 4 to 16 years were treated with VP-16 after neuroradiographic and clinical evidence of tumor progression. Six had received prior irradiation. All seven had been pretreated with a variety of chemotherapeutic agents and schedules, including parenteral VP-16. VP-16 was administered orally as repeated 21-day courses at 50 mg/m2/d with a 7-day interval between courses. Evaluation consisted of neuroradiographic and clinical examination after completion of every two courses of therapy. Complete blood cell counts were performed weekly. RESULTS The major toxicity of oral VP-16 was hematologic, with two patients requiring platelet transfusions due to thrombocytopenia and two requiring RBC transfusions. All seven patients developed treatment-related neutropenia. Two patients were supported with granulocyte colony-stimulating factor (G-CSF) between courses. One patient developed infectious epididymitis after course 2 and required intravenous antibiotics; this illness was complicated by Clostridium difficile colitis. There was one episode of fever associated with neutropenia. There were no treatment-related deaths. Of seven patients assessed, six have demonstrated partial responses (PRs) and the remaining patient had stable disease (SD). CONCLUSION This report demonstrates the activity of oral VP-16 in the treatment of a small cohort of pretreated patients with recurrent medulloblastoma. This form of administration of oral VP-16 was well tolerated and produced modest toxicity.
Utility of gallium-67 scintigraphy in low-grade non-Hodgkin's lymphoma.
Authors: Ben-Haim S , Bar-Shalom R , Israel O , Haim N , Epelbaum R , Ben-Shachar M , Gaitini D , Kolodny G M , Front D 
Published: February 2017

PURPOSE Low-grade non-Hodgkin's lymphoma (LGNHL) has traditionally been considered non-gallium-avid. The sensitivity of gallium 67 (67Ga) scintigraphy when using modern equipment and techniques in patients with LGNHL was investigated. MATERIALS AND METHODS Fifty-seven consecutive patients with LGNHL underwent 67Ga scintigraphy at initial presentation (n = 40), when tumor progression occurred during treatment (n = 3), and at suspected disease recurrence after continuous clinical remission (CCR) (n = 14). Planar and tomographic images were obtained with either a very large field-of-view or a dual-head digital camera. Of 45 patients with Ga-avid LGNHL, 30 underwent 93 follow-up scans (one to six studies per patient). Scan findings were correlated with clinical and computed tomographic (CT) findings and with patient outcomes. RESULTS 67Ga scintigraphy was positive in 45 of 57 patients (sensitivity, 79%) and in 113 of 164 disease sites (sensitivity, 69%). The sensitivity was higher in the more common types of LGNHL: follicular, predominantly small cleaved cell (FSC), and follicular, mixed small cleaved and large cell (FM) (84% and 91% in patients and 72% and 71% in disease sites, respectively). Sensitivity was lower in patients with mucosa-associated lymphoid tissue lymphoma (MALT) and small lymphocytic lymphoma (SL). Among 28 patients with disease recurrence after CCR (14 with and 14 without baseline studies), 67Ga scan was positive in 25, for a sensitivity of 89% for detection of disease recurrence. CONCLUSION When modern technology is used, 67Ga scintigraphy has good sensitivity in patients with LGNHL. It therefore can be used to monitor response to therapy and to provide early detection of disease recurrence in these patients.