bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of consecutive low-dose cisplatin with bleomycin, vincristine, and mitomycin for recurrent cervical carcinoma.
Authors: Shimizu Y , Akiyama F , Umezawa S , Ishiya T , Utsugi K , Hasumi K 
Published: February 2017

PURPOSE To evaluate the efficacy and toxicity of combination chemotherapy with bleomycin, vincristine, mitomycin, and consecutive low-dose (CLD) administration of cisplatin (CLD-BOMP) for patients with recurrent cervical carcinoma. PATIENTS AND METHODS Ninety patients with recurrent cervical carcinoma and no prior chemotherapy were enrolled onto this study. The median age was 56 years. Eighty-seven of the 90 patients had received prior radiotherapy. The CLD-BOMP regimen was bleomycin 5 mg infused continuously days 1 through 7; vincristine 0.7 mg/m2 bolus day 7; mitomycin 7 mg/m2 bolus day 7; and cisplatin 10 mg/m2 infused over 4 hours days 1 through 7. The treatment was repeated at 3-week intervals. RESULTS All 90 patients were assessable for response, toxicity, and survival. After a median of four cycles (range, two to 10 cycles), we observed objective responses in 68 patients (76%), with 25 (28%) complete responses (CRs) and 43 (48%) partial responses (PRs; 95% confidence interval (CI), 66 to 85; 18 to 38; 37 to 59, respectively). Median survival for all 90 patients was 24.3 months (range, 2.3 to 100 months). The median survival for patients who achieved CR, PR, no change (NC), and progressive disease (PD) were not reached (NR), 23.6, 8.2, and 6.4 months, respectively. The median progression-free survival for patients who achieved CR and PR were NR and 12.3 months, respectively. There was no significant nausea or vomiting, nephrotoxicity, or pulmonary toxicity, which was attributable to the CLD-cisplatin and the adequate dosing schedule of bleomycin. The reduced toxicities allowed this regimen to be administered at the projected dose-intensities. CONCLUSION The CLD-BOMP regimen has significant antitumor activity with markedly reduced toxicity.
Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group.
Authors: Hortobagyi G N , Theriault R L , Lipton A , Porter L , Blayney D , Sinoff C , Wheeler H , Simeone J F , Seaman J J , Knight R D , Heffernan M , Mellars K , Reitsma D J 
Published: February 2017

PURPOSE Pamidronate, an aminobisphosphonate, has been shown to lower the risk of skeletal complications associated with lytic bone lesions for up to 1 year in women with stage IV breast cancer who received chemotherapy. We studied the long-term effectiveness and safety of continued treatment with intravenous pamidronate infusions for up to 2 years. PATIENTS AND METHODS Three hundred eighty-two women with metastatic breast cancer and lytic bone lesions who received chemotherapy were randomly assigned to receive either 90 mg of pamidronate or placebo intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel-group trial. Patients were evaluated monthly for 2 years for skeletal complications, which included pathologic fractures, need for radiation or surgery to treat bone complications, spinal cord compression, and hypercalcemia. Bone pain, analgesic use, bone biochemical markers, performance status, quality of life, radiologic response in bone, and survival were also evaluated. RESULTS As in the first year of treatment, the proportion of patients with any skeletal complication was significantly less for the pamidronate than the placebo group at 15, 18, 21, and 24 months (P < .001). The proportions of patients with any pathologic fracture (i.e., vertebral and nonvertebral fractures), need for radiation or surgery to treat bone complications, and hypercalcemia were also statistically less for the pamidronate than the placebo group. The median time to the first skeletal complication was 13.9 months in the pamidronate-treated women and 7.0 months in the placebo group (P < .001). Long-term treatment did not result in any unexpected adverse events. Survival did not differ between the two groups. CONCLUSION The risk for osteolytic bone lesion complications in metastatic breast cancer was significantly decreased with monthly infusions of 90 mg of pamidronate, and this effect was maintained for at least 2 years. Pamidronate is a useful adjunct to standard chemotherapy in the palliative treatment of metastatic breast cancer.
First-cycle blood counts and subsequent neutropenia, dose reduction, or delay in early-stage breast cancer therapy.
Authors: Silber J H , Fridman M , DiPaola R S , Erder M H , Pauly M V , Fox K R 
Published: February 2017

PURPOSE If patients could be ranked according to their projected need for supportive care therapy, then more efficient and less costly treatment algorithms might be developed. This work reports on the construction of a model of neutropenia, dose reduction, or delay that rank-orders patients according to their need for costly supportive care such as granulocyte growth factors. PATIENTS AND METHODS A case series and consecutive sample of patients treated for breast cancer were studied. Patients had received standard-dose adjuvant chemotherapy for early-stage nonmetastatic breast cancer and were treated by four medical oncologists. Using 95 patients and validated with 80 additional patients, development models were constructed to predict one or more of the following events: neutropenia (absolute neutrophil count [ANC] < or = 250/microL), dose reduction > or = 15% of that scheduled, or treatment delay > or = 7 days. Two approaches to modeling were attempted. The pretreatment approach used only pretreatment predictors such as chemotherapy regimen and radiation history; the conditional approach included, in addition, blood count information obtained in the first cycle of treatment. RESULTS The pretreatment model was unsuccessful at predicting neutropenia, dose reduction, or delay (c-statistic = 0.63). Conditional models were good predictors of subsequent events after cycle 1 (c-statistic = 0.87 and 0.78 for development and validation samples, respectively). The depth of the first-cycle ANC was an excellent predictor of events in subsequent cycles (P = .0001 to .004). Chemotherapy plus radiation also increased the risk of subsequent events (P = .0011 to .0901). Decline in hemoglobin (HGB) level during the first cycle of therapy was a significant predictor of events in the development study (P = .0074 and .0015), and although the trend was similar in the validation study, HGB decline failed to reach statistical significance. CONCLUSION It is possible to rank patients according to their need of supportive care based on blood counts observed in the first cycle of therapy. Such rankings may aid in the choice of appropriate supportive care for patients with early-stage breast cancer.
Intensification of preoperative chemotherapy for osteogenic sarcoma: results of the Memorial Sloan-Kettering (T12) protocol.
Authors: Meyers P A , Gorlick R , Heller G , Casper E , Lane J , Huvos A G , Healey J H 
Published: February 2017

PURPOSE It has been observed previously in osteosarcoma (OS) that the degree of necrosis of the resected primary tumor following a period of preoperative chemotherapy is predictive of subsequent event-free survival (EFS). The aim of this study was to determine if more intensive preoperative chemotherapy would increase the proportion of patients with a good histologic response and improve EFS. PATIENTS AND METHODS Seventy-three patients with OS were treated at Memorial-Sloan Kettering Cancer Center (MSKCC) on the T12 protocol between 1986 and 1993. Patients were randomized between therapy based on the T10 protocol and therapy with more intensive preoperative chemotherapy. The more intensive preoperative regimen consisted of two courses of cisplatin (CDDP) and doxorubicin (DOX) in addition to the usual preoperative regimen of high-dose methotrexate (HD MTX) and bleomycin, cyclophosphamide, and dactinomycin (BCD). RESULTS The regimen with more intensive preoperative chemotherapy achieved a modest increase in the proportion of patients with a good histologic response (44% with a grade III or IV histologic response v 37% in the control arm, 33% with grade IV histologic response v 13% in the control arm). EFS continued to correlate with histologic response. The actuarial 5-year EFS in patients with localized disease was 78% for the regimen with more intensive preoperative chemotherapy and 73% for the control arm. CONCLUSION Despite modest increases in the proportion of patients with good histologic response with intensified preoperative chemotherapy, no improvement in EFS was observed.
Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications.
Authors: Kwiatkowski D J , Harpole D H , Godleski J , Herndon J E , Shieh D B , Richards W , Blanco R , Xu H J , Strauss G M , Sugarbaker D J 
Published: February 2017

PURPOSE To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design a molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). METHODS All patients with stage I NSCLC resected at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-up were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. RESULTS Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge resection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection, tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. CONCLUSION Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors for recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded Ia, with a 5-year CFS rate of 87%; those with three factors are graded Ib, with a 5-year CFS rate of 58%; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21%.
Phase I trial of 9-aminocamptothecin in children with refractory solid tumors: a Pediatric Oncology Group study.
Authors: Langevin A M , Casto D T , Thomas P J , Weitman S D , Kretschmar C , Grier H , Pratt C , Dubowy R , Bernstein M , Blaney S , Vietti T 
Published: February 2017

PURPOSE A phase I trial of 9-aminocamptothecin (9-AC) was performed in children with solid tumors to establish the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and the pharmacokinetic profile in children and to document any evidence of activity. PATIENTS AND METHODS A 72-hour infusion of 9-AC dimethylacetamide formulation was administered every 21 days to 23 patients younger than 21 years of age with malignant tumors refractory to conventional therapy. Doses ranged from 36 to 62 microg/m2 per hour. Pharmacokinetics were to be performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. RESULTS Nineteen patients on four dose levels were assessable for toxicities. At 62 microg/m2 per hour, three patients experienced dose-limiting neutropenia and one patient experienced dose-limiting thrombocytopenia. Pharmacokinetics were performed on 15 patients (nine patients had complete sets of plasma sampling performed). The pharmacokinetics of both lactone and total 9-AC were highly variable. The percentage of 9-AC lactone at steady-state was 10.8% +/- 3.6%. Total 9-AC and its lactone form had a terminal half-life of 8.1 +/- 3.8 and 7.1 +/- 3.9 hours, respectively, and a volume of distribution at steady-state (Vdss) of 21.2 +/- 13.3 L/m2 and 135.3 +/- 52.5 L/m2, respectively. Hepatic metabolism and biliary transport had an important role in 9-AC disposition. CONCLUSION The recommended phase II dose of 9-AC administered as a 72-hour infusion every 21 days to children with solid tumors is 52 microg/m2 per hour. Neutropenia and thrombocytopenia were dose limiting.
Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment.
Authors: Pegram M D , Lipton A , Hayes D F , Weber B L , Baselga J M , Tripathy D , Baly D , Baughman S A , Twaddell T , Glaspy J A , Slamon D J 
Published: February 2017

PURPOSE To determine the toxicity, pharmacokinetics, response rate, and response duration of intravenous (i.v.) administration of recombinant, humanized anti-p185HER2 monoclonal antibody (rhuMAb HER2) plus cisplatin (CDDP) in a phase II, open-label, multicenter clinical trial for patients with HER2/neu-overexpressing metastatic breast cancer. PATIENTS AND METHODS The study population consisted of extensively pretreated advanced breast cancer patients with HER2/neu overexpression and disease progression during standard chemotherapy. Patients received a loading dose of rhuMAb HER2 (250 mg i.v.) on day 0, followed by weekly doses of 100 mg i.v. for 9 weeks. Patients received CDDP (75 mg/m2) on days 1, 29, and 57. RESULTS Of 37 patients assessable for response, nine (24.3%) achieved a PR, nine (24.3%) had a minor response or stable disease, and disease progression occurred in 19 (51.3%). The median response duration was 5.3 months (range, 1.6-18). Grade III or IV toxicity was observed in 22 of 39 patients (56%). The toxicity profile reflected that expected from CDDP alone with the most common toxicities being cytopenias (n = 10), nausea/vomiting (n = 9), and asthenia (n = 5). Mean pharmacokinetic parameters of rhuMAb HER2 were unaltered by coadministration of CDDP. CONCLUSION The use of rhuMAb HER2 in combination with CDDP in patients with HER2/neu-overexpressing metastatic breast cancer results in objective clinical response rates higher than those reported previously for CDDP alone, or rhuMAb HER2 alone. In addition, the combination results in no apparent increase in toxicity. Finally, the pharmacology of rhuMAb HER2 was unaffected by coadministration with CDDP.
Infiltrating ductal carcinoma of the breast: the survival impact of race.
Authors: Edwards M J , Gamel J W , Vaughan W P , Wrightson W R 
Published: February 2017

PURPOSE Breast cancer has a poorer prognosis among black women than among white women. This review was conducted to determine whether this disparity reflects the direct impact of race on likelihood of cure or on time to death from breast cancer or stems from the interaction of race with tumor stage and patient age. PATIENTS AND METHODS We analyzed data from 115,838 patients with localized (node-negative) and regionally metastatic (node-positive) breast cancer from the Surveillance, Epidemiology, and End-Results (SEER) Program of the National Cancer Institute. Parametric analysis was used to determine the independent prognostic value of age, stage, and race. Linear regression and distribution analyses were also used to examine the interaction of these covariates. RESULTS The prevalence of regionally metastatic disease, relative to localized disease, declined with increased age among white patients and those classified as "other," but remained relatively constant among black patients. Parametric analysis showed a smaller cured fraction and shorter time to death when patients with regional disease were compared with those with localized disease. A similar disparity was found when black patients were compared with those classified as white or other. CONCLUSION Age and race have a significant association with tumor stage. In addition, our data show that race has an independent impact on the clinical course of breast cancer and diminishes both the likelihood of cure and time to death among uncured patients.
Enhanced myelotoxicity due to granulocyte colony-stimulating factor administration until 48 hours before the next chemotherapy course in patients with small-cell lung carcinoma.
Authors: Tjan-Heijnen V C , Biesma B , Festen J , Splinter T A , Cox A , Wagener D J , Postmus P E 
Published: February 2017

PURPOSE To evaluate the impact of granulocyte colony-stimulating factor (G-CSF) priming on peripheral-blood cell counts during standard-dose chemotherapy. PATIENTS AND METHODS Twelve patients with relapsed small-cell lung carcinoma (SCLC) were treated with two chemotherapy courses. Six patients received G-CSF priming only before the first course (group A) and the other six patients only before the second course (group B). Each patient served as his own control. Patients were treated with cyclophosphamide, epirubicin, and etoposide (CEE), or with vincristine, ifosfamide, mesna, and carboplatin (VIMP) every 4 weeks. G-CSF was administered subcutaneously 5 microg/kg/d for 6 days until 48 hours before the first or second chemotherapy course. RESULTS Priming caused a lowering of the WBC nadir, with a median value of 0.95 x 10(9)/L (P = .004), and of absolute neutrophil nadir, with a median value of 0.48 x 10(9)/L (P = .03). There was a trend for a lower platelet (PLT) nadir after G-CSF priming (P = .09). G-CSF priming resulted in a prolonged duration of WBC count less than 3.0 x 10(9)/L of +4.25 days (P = .04), and of WBC count less than 1.0 x 10(9)/L of +0.50 days (P = .03). The duration of neutropenia less than 0.5 x 10(9)/L seemed longer in primed courses (+3.75 days, P = .18). The duration of PLT counts less than 100 x 10(9)/L was prolonged by 1.5 days (P = .04). Hemoglobin (Hgb) levels were not influenced by G-CSF priming. CONCLUSION G-CSF administration until 48 hours before the next chemotherapy course increases chemotherapy-associated leukocytopenia and thrombocytopenia. This may be of special concern when G-CSF is administered during dose-densified chemotherapy.
Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial.
Authors: Bajorin D F , McCaffrey J A , Hilton S , Mazumdar M , Kelly W K , Scher H I , Spicer J , Herr H , Higgins G 
Published: February 2017

PURPOSE A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.
Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.
Authors: Bécouarn Y , Ychou M , Ducreux M , Borel C , Bertheault-Cvitkovic F , Seitz J F , Nasca S , Nguyen T D , Paillot B , Raoul J L , Duffour J , Fandi A , Dupont-André G , Rougier P 
Published: February 2017

PURPOSE To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.