bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative abdominopelvic computed tomographic prediction of optimal cytoreduction in epithelial ovarian carcinoma.
Authors: Nelson B E , Rosenfield A T , Schwartz P E 
Published: February 2017

PURPOSE This study was undertaken to assess the ability of computed tomography (CT) to predict the likelihood of optimal primary tumor cytoreduction in women with epithelial ovarian carcinoma. PATIENTS AND METHODS Fifty-one women with preoperative CT and a histologic diagnosis of epithelial ovarian carcinoma following primary tumor operation by a gynecologic oncologist were identified. Forty-two CT scans were retrospectively analyzed. CT findings of attachment of the omentum to the spleen or disease greater than 2 cm on the diaphragm, liver surface, or parenchyma, pleura, mesentery, gallbladder fossa, or suprarenal paraaortic nodes were coded to represent unresectable disease. CT results were compared with surgical outcome. RESULTS Twenty-nine of 42 (69%) patients underwent optimal cytoreduction to less than 2 cm residual disease. Successful cytoreduction was accomplished in 23 of 24 patients who fulfilled CT criteria for cytoreduction and six of 18 with CT criteria predictive of inability to perform cytoreduction. CT was highly sensitive for detection of ascites, mesenteric, and omental disease, but was poor for detection of liver involvement, omental attachment to the spleen, gallbladder fossa disease, and peritoneal nodules smaller than 2 cm. The CT findings accurately predicted surgical outcome with a sensitivity of 92.3% and specificity of 79.3%. The positive predictive value was 67% and the negative predictive value was 96%. CONCLUSION CT scan is an accurate method for the prediction of successful surgical cytoreduction and may have utility in the decision to offer neoadjuvant chemotherapy to certain medically disabled patients, a hypothesis currently under evaluation.
Ifosfamide, mesna, and nephrotoxicity in children.
Authors: Skinner R , Sharkey I M , Pearson A D , Craft A W 
Published: February 2017

PURPOSE With the increasing use of ifosfamide in pediatric malignancies, nephrotoxicity has emerged as a potentially serious adverse effect, which may be dose-limiting or may cause severe chronic morbidity, including glomerular impairment and/or Fanconi's syndrome. The purpose of this review was (1) to improve the documentation of ifosfamide nephrotoxicity in children, and (2) to consider the possible causative role of ifosfamide metabolites. DESIGN (1) A grading system was developed that allowed documentation of the nature and severity of published reports of ifosfamide-induced nephrotoxicity, and evaluation of patient and treatment-related risk factors. (2) The relationship between the pharmacology of ifosfamide/mesna and nephrotoxicity was investigated by examination of published data, especially that concerning the quantitative differences in the metabolism of ifosfamide and its nonnephrotoxic structural isomer, cyclophosphamide. RESULTS (1) Examination of 16 published reports (with assessable data from 40 children) demonstrated that ifosfamide-induced nephrotoxicity was associated with a wide range of patient ages and ifosfamide cumulative doses given by different administration schedules. (2) Chloroacetaldehyde, a major metabolite of ifosfamide only, may be at least partly responsible for the renal toxicity of this drug. Although mesna may be capable of detoxifying the toxic metabolite(s), delivery to the renal tubule may not be sufficient to provide adequate protection of tubular glutathione from depletion by the metabolite(s), which results in a failure to prevent nephrotoxicity. CONCLUSION Increased understanding of the interindividual variability in the extent and nature of ifosfamide metabolism, which may be a major determinant of susceptibility to renal damage, may lead to improved use of the drug with less nephrotoxicity.
Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction.
Authors: Ajani J A , Roth J A , Ryan M B , Putnam J B , Pazdur R , Levin B , Gutterman J U , McMurtrey M 
Published: February 2017

PURPOSE The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression. PATIENTS AND METHODS Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy. RESULTS A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated. CONCLUSION High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.
Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.
Authors: Paterson A H , Powles T J , Kanis J A , McCloskey E , Hanson J , Ashley S 
Published: February 2017

PURPOSE Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer. PATIENTS AND METHODS We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients). RESULTS The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups. CONCLUSIONS These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.
The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03.
Authors: Wolmark N , Rockette H , Fisher B , Wickerham D L , Redmond C , Fisher E R , Jones J , Mamounas E P , Ore L , Petrelli N J 
Published: February 2017

PURPOSE This study was designed to evaluate the efficacy of leucovorin-modulated fluorouracil (5-FU) as adjuvant therapy for patients with Dukes' stage B and C colon cancer. PATIENTS AND METHODS Data are presented from 1,081 patients with Dukes' stage B and C carcinoma of the colon entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 between August 1987 and April 1989. Patients were randomly assigned to receive either lomustine (MeCCNU), vincristine, and 5-FU (MOF), or leucovorin-modulated 5-FU (LV + 5-FU). The mean time on study was 47.6 months. RESULTS Comparison between the two groups indicates a disease-free survival advantage for patients treated with LV + 5-FU (P = .0004). The 3-year disease-free survival rate for patients in this group was 73% (95% confidence interval, 69% to 77%), compared with 64% (95% confidence interval, 60% to 68%) for patients receiving MOF. The corresponding percentage of patients surviving was 84% for those randomized to receive LV + 5-FU and 77% for the MOF-treated cohort (P = .003). At 3 years of follow-up, patients treated with postoperative LV + 5-FU had a 30% reduction in the risk of developing a treatment failure and a 32% reduction in mortality risk compared with similar patients treated with MOF. CONCLUSION Treatment with LV + 5-FU significantly prolongs disease-free survival and results in a significant benefit relative to overall survival. These findings, when considered together with results from a recent meta-analysis demonstrating a benefit from LV + 5-FU in advanced disease, provide evidence to support the concept of metabolic modulation of 5-FU.
Total-body irradiation and autologous bone marrow transplant in the treatment of high-risk Ewing's sarcoma and rhabdomyosarcoma.
Authors: Horowitz M E , Kinsella T J , Wexler L H , Belasco J , Triche T , Tsokos M , Steinberg S M , McClure L , Longo D L , Steis R G 
Published: February 2017

PURPOSE In an effort to improve outcome in patients with metastatic or high-risk localized Ewing's sarcoma family of tumors (ESF) and rhabdomyosarcoma (RMS), we explored the role of consolidation therapy with total-body irradiation (TBI) plus autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS Ninety-one patients were entered onto one of three consecutive protocols from 1981 to 1986. Induction therapy consisted of four or five cycles of vincristine, doxorubicin, and cyclophosphamide (VAdriaC); in the earlier series, patients received one or two cycles with dactinomycin instead of doxorubicin. Irradiation of the primary site was used for local control. Patients who attained a complete response (CR) to induction therapy were eligible for consolidation with 8 Gy TBI plus VAdriaC and ABMT. RESULTS Nineteen patients were ineligible for consolidation after failing to achieve or maintain a CR following induction therapy; all 19 are dead of disease. Seven eligible patients elected to forgo consolidation; three of seven are long-term event-free survivors. Sixty-five patients received consolidation therapy; 20 of 65 are long-term event-free survivors. A local control rate of 83% was achieved using radiation therapy as the primary modality of local control. Patients with metastatic disease at diagnosis fared substantially worse than did patients with localized tumors (6-year event-free survival [EFS] rate, 14% v 38%; two-sided P [P2] = .008). CONCLUSIONS Consolidation of patients with metastatic or high-risk localized pediatric sarcomas with 8 Gy TBI plus ABMT has failed to improve the outcome of this group of patients. Metastatic disease at diagnosis continues to confer the poorest prognosis. New therapeutic strategies are needed to consolidate more effectively the remissions that can be achieved in the majority of these patients.
Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group.
Authors: Seshadri R , Firgaira F A , Horsfall D J , McCaul K , Setlur V , Kitchen P 
Published: February 2017

PURPOSE To determine prospectively the prognostic significance of HER-2/neu oncogene amplification in the primary tumors of breast cancer patients. METHODS HER-2/neu amplification in tumor DNA was determined by the slot-blot technique in 1,056 patients with breast cancer (stage I to III) diagnosed between 1987 and 1990. Parameters such as estrogen receptor (ER) and progesterone receptor (PgR) levels, tumor size, axillary nodal involvement, tumor grade, and time to relapse were prospectively obtained. RESULTS HER-2/neu oncogene amplification, > or = 2, > or = 3, and > or = 5 copy number, was detected in 21%, 11%, and 7% of patients, respectively. In a test set of 529 patients, Cox multivariate analysis showed HER-2/neu copy number > or = 3 or > or = 5 was associated with shorter disease-free survival (DFS) duration. HER-2/neu copy number > or = 3 correlated significantly with pathologic stage of disease, number of axillary nodes with tumor, histologic type, and absence of ER and PgR. For all patients, after a median follow-up duration of 39 months, Kaplan-Meier univariate analysis indicated that tumor oncogene copy number > or = 3 correlated with shorter DFS in both node-negative and node-positive patients. In Cox multivariate analysis, HER-2/neu copy number > or = 3 was associated with shorter DFS, independent of nodal status, ER level, and tumor size. CONCLUSION Although the follow-up duration of this study is relatively short, we conclude that HER-2/neu amplification is an independent predictor of shorter DFS in both node-negative and node-positive patients.
Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting.
Authors: Rowinsky E K , Chaudhry V , Forastiere A A , Sartorius S E , Ettinger D S , Grochow L B , Lubejko B G , Cornblath D R , Donehower R C 
Published: February 2017

PURPOSE To determine the maximum-tolerated doses (MTD), the principal toxicities, and the pharmacologic behavior of high doses of Taxol (paclitaxel; Bristol-Myers Squibb, New York, NY) combined with cisplatin and granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS Untreated and minimally pretreated solid-tumor patients received 24-hour infusions of Taxol on day 1 followed by cisplatin on day 2 and G-CSF, 5 micrograms/kg/d subcutaneously (SC), beginning on day 3. Treatment was repeated every 3 weeks. Starting doses of Taxol and cisplatin were 135 and 75 mg/m2, respectively. RESULTS The development of a severe peripheral neuropathy and/or severe myalgias precluded the chronic administration of Taxol and cisplatin with G-CSF at doses greater than 250 mg/m2 and 75 mg/m2, respectively. At this dose, the mean Taxol steady-state plasma concentration (Css) exceeds concentrations capable of inducing pertinent antimicrotubule effects in vitro. The severity of the neuropathy was related to the cumulative dose of Taxol, the magnitude of the dose administered during each treatment, and the presence of a pre-existing medical disorder associated with peripheral neuropathy. A proximal myopathy of modest severity also was documented. Although severe neutropenia occurred frequently, especially at the MTD, it was rarely associated with fever (8% of courses), and absolute neutrophil counts (ANCs) less than 500/microL never persisted for more than 5 days. Responses were noted in non-small-cell lung cancer (NSCLC) and head and neck, breast, and esophageal cancers. CONCLUSION Taxol and cisplatin doses of 250 mg/m2 and 75 mg/m2, respectively, can be administered repetitively with G-CSF to untreated and minimally pretreated patients. However, these doses are not recommended for patients with pre-existing neuropathies until additional experience in high-risk patients is obtained. Although this Taxol dose is nearly 85% higher than the dose that can be combined with cisplatin in the absence of G-CSF, this high-dose regimen should not be used outside the investigational setting until a dose-response relationship has been demonstrated for Taxol in randomized clinical trials.
Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma.
Authors: Czuczman M S , Straus D J , Divgi C R , Graham M , Garin-Chesa P , Finn R , Myers J , Old L J , Larson S M , Scheinberg D A 
Published: February 2017

PURPOSE Eighteen patients with recurrent or refractory CD21-positive, non-Hodgkin's lymphoma (NHL) were treated in a phase IA dose-escalation therapeutic trial of iodine 131 labeled to a fixed dose of OKB7. METHODS Individual doses of 30 to 50 mCi of 131I on 25 mg OKB7 were administered 2 to 3 days apart to achieve four total 131I-OKB7 dose levels of 90, 120, 160, and 200 mCi. Pharmacology, dosimetry, therapeutic effects, toxicity, human anti-mouse antibody (HAMA) response, and maximum-tolerated dose (MTD) were determined. Patients were evaluated by imaging studies (including whole-body gamma camera or single-photon emission computed tomography [SPECT] scans), flow cytometric analysis, bone marrow biopsy, and serial blood sampling. RESULTS Median plasma and whole-body half-lives (T1/2) were 16 hours and 14 hours, respectively. Plasma and whole-body radiation doses were 0.0081 Gy/mCi and 0.0022 Gy/mCi, respectively. Specific tumor visualization was noted in eight of 18 patients. HAMA was detected in 12 of 16 patients. Nonhematologic toxicity was limited to asymptomatic elevations of thyroid-stimulating hormone (TSH) in five of 15 patients. Hematologic toxicity was observed in six of 18 patients, but was severe in only two patients. MTD in patients with diffuse lymphomatous bone marrow involvement was determined to be 200 mCi in four divided doses of 50 mCi 131I/25 mg OKB7. Antitumor activity was observed in 13 of 18 patients (one partial response [PR] and 12 mixed responses) and was dependent on the 131I-OKB7 dose administered. In general, palpable peripheral lymphadenopathy, enlarged spleens, skin lesions, and circulating OKB7-positive peripheral lymphocytes responded most readily to treatment. 131I-OKB7 was safely administered to a patient in leukemic phase of NHL with prompt subsequent loss of approximately 1 kg of tumor cells from the peripheral blood without associated tumor lysis syndrome. CONCLUSION Because antitumor activity with tolerable toxicity was observed in the majority of this group of heavily pretreated patients, phase II investigation of mAb OKB7 radioconjugates in the therapy of NHL is warranted.
Pharmacokinetics of paclitaxel and metabolites in a randomized comparative study in platinum-pretreated ovarian cancer patients.
Authors: Huizing M T , Keung A C , Rosing H , van der Kuij V , ten Bokkel Huinink W W , Mandjes I M , Dubbelman A C , Pinedo H M , Beijnen J H 
Published: February 2017

PURPOSE To investigate the pharmacokinetics and pharmacodynamics of paclitaxel in a randomized comparative study with four different treatment arms in patients with platinum-pretreated ovarian carcinoma. PATIENTS AND METHODS Eighteen patients were entered onto this study in which paclitaxel was administered at a high dose of 175 mg/m2 versus a low dose of 135 mg/m2 on a 3- or 24-hour infusion schedule. A solid-phase extraction technique for sample pretreatment followed by a reverse-phase high-performance liquid chromatographic (HPLC) assay was used for analysis of plasma. RESULTS Grade 3 neutropenia occurred in all four treatment arms. However, it was more severe on the 24-hour infusion schedule. Paclitaxel concentrations as low as 0.012 mumol/L were measured with the HPLC assay. With this low quantitation threshold, we found the plasma disappearance of paclitaxel to be triphasic, with half-lives t1/2(alpha), t1/2(beta), and t1/2(gamma) mean values for the different treatment arms of 0.19 hours (range, 0.01 to 0.4), 1.9 hours (range, 0.5 to 2.8), and 20.7 hours (range, 4 to 65), respectively. Eleven possible metabolites were found, of which three were identified as taxanes by on-line HPLC-photodiode array (PDA) detection. Investigation of pharmacodynamics shows no clear relationship between the pharmacokinetic parameters area under the plasma concentration time curve (AUC), area under the plasma concentration moment curve (AUMC), maximal plasma concentration (Cmax), clearance, and toxicity. However, a relationship was found between the duration of plasma concentrations above a threshold of 0.1 mumol/L with absolute neutrophil count (ANC) and white blood cell count (WBC). CONCLUSION Paclitaxel is metabolized, and putative metabolic products can be found in plasma of patients treated with the drug. Our results indicate that myelosuppression can be predicted by the measurement of the duration of plasma concentrations above the threshold of 0.1 mumol/L.
Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study.
Authors: Housset M , Maulard C , Chretien Y , Dufour B , Delanian S , Huart J , Colardelle F , Brunel P , Baillet F 
Published: February 2017

PURPOSE To improve the results obtained by cystectomy alone and to determine the possibilities of conservative treatment in invasive bladder cancer, we designed a prospective study using a combination of fluorouracil (5-FU) plus cisplatin and concomitant radiation therapy, followed by either cystectomy or additional chemoradiotherapy. PATIENTS AND METHODS Fifty-four patients with stage T2 to T4 operable untreated invasive bladder cancer were entered onto the study. Treatment was begun in all patients by transurethral resection (TUR) and followed by the 5-FU-cisplatin combination with concomitant bifractionated split-course radiation therapy. A control cystoscopy was performed 6 weeks after completion of the neoadjuvant program. Patients with persistent tumor underwent cystectomy. Complete responders were treated by either additional chemoradiotherapy (group A) or cystectomy (group B). RESULTS At control cystoscopy, 40 of 54 patients (74%) had a histologically documented complete response. Four responders developed recurrent pelvic disease after a mean follow-up time of 27 +/- 12 months (three in group A and one in group B). Metastatic disease, which developed in 16 patients, occurred more frequently in the nonresponders (71%) than in responders (15%). The disease-free survival rate at 3 years was 62%; it was significantly better in responders (77%) than in nonresponders (23%). There was no difference in survival between groups A and B. CONCLUSION This neoadjuvant chemoradiotherapy combination, easy to implement and well tolerated even in elderly patients, provides a high complete response rate. It may prove to be effective in inoperable patients and may be proposed as conservative treatment in patients with a complete response to the initial course of chemoradiation.