bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outpatient high-dose chemotherapy with autologous stem-cell rescue for hematologic and nonhematologic malignancies.
Authors: Meisenberg B R , Miller W E , McMillan R , Callaghan M , Sloan C , Brehm T , Kosty M P , Kroener J , Longmire R , Saven A , Piro L D 
Published: February 2017

PURPOSE A prospective study to determine the feasibility of high-dose chemotherapy (HDC) and autologous stem-cell rescue (ASCR) in the outpatient setting. METHODS One hundred thirteen consecutive patients underwent 165 cycles of HDC/ASCR for a variety of malignancies. HDC regimens were disease-specific. Initially, patients were hospitalized for HDC, discharged on completion, and maintained as outpatients unless toxicities required rehospitalization (subtotal outpatient transplantation [STOT]). Once this was established as safe, a total outpatient transplant (TOT) program was developed in which patients received all of the HDC, as well as supportive care, as outpatients. Patients who declined the outpatient programs received the same HDC and supportive care as inpatients. RESULTS In 140 of 165 (85%) HDC cycles, patients agreed to participate in one of the outpatient transplant programs. Five patients in the STOT program could not be discharged from the hospital because of toxicities that developed during HDC; thus, 135 patients were monitored the outpatient setting, 95 (70%) of whom were never readmitted. The mean +/- SEM total hospital length of stay (LOS), including all readmissions and excess days after chemotherapy, was 18.33 +/- 5.06 days for patients who refused the outpatient program, 8.22 +/- 5.76 days for patients in the STOT program, and 2.81 +/- 7.66 days for those in the TOT program (P < .001). One treatment-related death occurred in each treatment setting: day 120 inpatient, day 17 STOT, and day 110 TOT. CONCLUSION Outpatient management of HDC/ASCR is safe and acceptable for the vast majority of patients. The STOT program resulted in significant reduction in hospital LOS, while the TOT program appears equally safe and further reduces LOS. Hospitalization for HDC/ASCR is unnecessary in most patients.
Patient preferences for oral versus intravenous palliative chemotherapy.
Authors: Liu G , Franssen E , Fitch M I , Warner E 
Published: February 2017

PURPOSE To assess patient preference for oral versus intravenous (i.v.) palliative chemotherapy (CT). A strong preference would be an important quality-of-life issue. PATIENTS AND METHODS A structured interviewer-administered scenario-based questionnaire evaluated incurable cancer patients who would be likely to receive palliative CT in the future. Using probability trade-offs, the preference for route of administration was evaluated against diminishing treatment response. RESULTS Of 103 assessable patients, 92 preferred oral CT, 10 preferred i.v. CT, and one had no preference. Patient preferences were not associated with age, sex, site of primary cancer, or previous CT experiences. Major reasons for preferring oral CT were convenience, problems with i.v. access or needles, and a better CT-taking environment (outside of the clinic). Regardless of initial preference, 70% of patients were not willing to accept a lower response rate and 74% were not willing to accept a shorter duration of response to retain their initial preference. Although 99% of patients had a preference, 39% wanted the specific treatment decision made primarily by their physicians, 38% primarily by themselves, and 22% shared equally. CONCLUSION Patients with incurable cancer have a clear preference for oral CT, but are generally not willing to sacrifice efficacy for their preference. Almost 40% of patients did not want to make final treatment decisions themselves.
Evaluation of new bone resorption markers in a randomized comparison of pamidronate or clodronate for hypercalcemia of malignancy.
Authors: Vinholes J , Guo C Y , Purohit O P , Eastell R , Coleman R E 
Published: February 2017

PURPOSE To compare the effects of two bisphosphonates on markers of bone resorption in a randomized double-blind trial for the treatment of hypercalcemia of malignancy. PATIENTS AND METHODS Thirty-two patients with a serum calcium (sCa) level > or = 2.7 mmol/L that persisted after 48 hours of saline rehydration were randomized to receive pamidronate 90 mg or clodronate 1,500 mg. Bone resorption markers measured included urinary calcium (uCa), hydroxyproline (Hyp), deoxypyridinoline (Dpd), pyridinoline (Pyd), the cross-linking molecule at either the N-telopeptide (NTx) or the C-telopeptide (Crosslaps) regions of type I collagen, and free Dpd. RESULTS Both bisphosphonates restored normocalcemia, but the duration of action was longer after pamidronate (P < .01). There was a mean pretreatment sevenfold increase in NTx, fivefold increase in Dpd and Crosslaps, and 2.5-fold increase in free Dpd. The changes in uCa were confounded by an increase in parathyroid hormone (PTH) (P < .05), which, through effects on the kidney, inhibits calcium excretion. Most resorption markers showed a larger decrease after pamidronate than clodronate (P < .01). NTx and Crosslaps showed the greatest decrease, being significantly different from any other marker in both arms (P < .01). There was a significant correlation between Dpd, NTx, and Crosslaps (P < .002), but not with uCa. CONCLUSION The superiority of pamidronate in controlling hypercalcemia is mirrored by the changes observed in these markers. uCa is not an accurate bone resorption marker, which reflects the renal handling of calcium by PTH. NTx and Crosslaps showed the largest increase at baseline and the greatest change after treatment, which suggests these new markers may be more sensitive indicators of bone resorption.
Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery.
Authors: Caillot D , Casasnovas O , Bernard A , Couaillier J F , Durand C , Cuisenier B , Solary E , Piard F , Petrella T , Bonnin A , Couillault G , Dumas M , Guy H 
Published: February 2017

PURPOSE The prognosis of invasive pulmonary aspergillosis (IPA) occurring in neutropenic patients remains poor. We studied whether new strategies for early diagnosis could improve outcome in these patients. PATIENTS AND METHODS Twenty-three histologically proven and 14 highly probable IPAs in 37 hematologic patients (neutropenic in 36) were analyzed retrospectively. RESULTS The most frequent clinical signs associated with IPA were cough (92%), chest pain (76%), and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32 cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL fluid. Since October 1991, early thoracic computed tomographic (CT) scans were systematically performed in febrile neutropenic patients with pulmonary x-ray infiltrates. This approach allowed us to recognize suggestive CT halo signs in 92% of patients, compared with 13% before this date, and the mean time to IPA diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable patients, 10 failed to respond (amphotericin B [AmB] plus fluorocytosyne, n = 2; itraconazole + AmB, n = 8) and died of aspergillosis. Twenty-six patients were cured or improved by antifungal treatment (itraconazole with or without AmB, n = 22; voriconazole, n = 4). In 15 of 16 cases, surgical resection was combined successfully with medical treatment. Achievement of hematologic response, early diagnosis, unilateral pulmonary involvement, and highest level of fibrinogen value < 9 g/L were associated with better outcome. CONCLUSION In febrile neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early antifungal treatment, combined with surgical resection if necessary, improves IPA prognosis dramatically in these patients.
Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study.
Authors: Omura G A , Blessing J A , Vaccarello L , Berman M L , Clarke-Pearson D L , Mutch D G , Anderson B 
Published: February 2017

PURPOSE Cisplatin, mitolactol (dibromodulcitol), and ifosfamide have been the most active single agents in squamous carcinoma of the cervix identified so far by the Gynecologic Oncology Group (GOG). Combinations of cisplatin plus ifosfamide and cisplatin plus mitolactol are prospectively compared with cisplatin alone. PATIENTS AND METHODS Patients were randomized to receive cisplatin 50 mg/m2 or the same dose of cisplatin plus mitolactol (C + M) 180 mg/m2 orally on days 2 to 6, or cisplatin plus ifosfamide (CIFX) 5 g/m2 given as a 24-hour infusion plus mesna 6 g/m2 during and for 12 hours after the ifosfamide infusion, every 3 weeks for up to six courses. Of 454 patients entered, 438 were eligible and analyzed for response and survival. RESULTS CIFX had a higher response rate (31.1% v 17.8%, p = .004) and longer progression-free survival (PFS) time (P = .003) compared with cisplatin alone. The median times to progression or death were 4.6 and 3.2 months, respectively. C + M showed no significant improvement in these parameters compared with cisplatin alone. Survival was associated with initial performance score (PS; 0 was more favorable; P < .001) and with age (younger was unfavorable, P = .025). There was no significant difference in overall survival between cisplatin and either of the combinations. Leukopenia, renal toxicity, peripheral neurotoxicity, and CNS toxicity were more frequent with CIFX (P < .05). CONCLUSION CIFX improved the response rate and PFS duration in advanced cervix cancer compared with cisplatin alone, but at the cost of greater toxicity and with no improvement in survival.
Mutational activation of the K-ras oncogene and the effect of chemotherapy in advanced adenocarcinoma of the lung: a prospective study.
Authors: Rodenhuis S , Boerrigter L , Top B , Slebos R J , Mooi W J , van't Veer L , van Zandwijk N 
Published: February 2017

PURPOSE To determine whether the clinical course and the response to chemotherapy of patients with advanced adenocarcinoma of the lung depends on the presence or absence of a ras mutation in the tumor. Mutational activation of K-ras is a strong adverse prognostic factor in stage I or II lung cancer and laboratory studies have suggested that ras mutations lead to resistance against ionizing radiation and chemotherapy. PATIENTS AND METHODS Patients with advanced adenocarcinoma of the lung with measurable or assessable disease received chemotherapy with mesna, ifosfamide, carboplatin, and etoposide (MICE). Archival biopsies, fresh biopsies, or fine-needle aspirations were tested for the presence of ras gene mutations. Associations of ras mutations with clinical characteristics, response to chemotherapy, and survival were studied. RESULTS The presence or absence of ras gene mutations could be established in 69 of 83 patients (83%). A total of 261 courses of MICE were administered to 62 informative patients, 16 of whom were shown to have a K-ras mutation-positive tumor. The frequency of mutations (26%) and the type of mutations closely matched the pattern we have previously reported in operable disease. Patients with a ras mutation in their tumor were more likely to have a close relative with lung cancer, but other clinical characteristics, such as pattern of metastases, response, and survival, were similar between the ras mutation-positive and ras mutation-negative groups. CONCLUSION Patients with advanced lung adenocarcinoma who harbor a ras mutation may have major responses to chemotherapy and have similar progression-free and overall survival as patients with ras mutation-negative tumors. K-ras mutations may represent one of several ways in which early tumors are enabled to metastasize to distant sites.
Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer.
Authors: Oshita F , Noda K , Nishiwaki Y , Fujita A , Kurita Y , Nakabayashi T , Tobise K , Abe S , Suzuki S , Hayashi I , Kawakami Y , Matsuda T , Tsuchiya S , Takahashi S , Tamura T , Saijo N 
Published: February 2017

PURPOSE To determine the effects of irinotecan (CPT-11) given in combination with etoposide (VP-16) in metastatic non-small-cell lung cancer (NSCLC), to evaluate response and survival rates, and to determine the qualitative and quantitative toxicities of the combination chemotherapy. PATIENTS AND METHODS Sixty-one metastatic NSCLC patients received concurrent administration of CPT-11 and VP-16 for 3 days with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support. RESULTS Fifty-nine patients were assessable for response and all 61 patients were assessable for toxicity and survival. Fifty-six patients were treated with two or more courses of chemotherapy. Thirteen patients achieved a partial response (PR), 36 showed no change (NC), and 10 showed progressive disease (PD). The overall response rate was 21.3% (95% confidence interval, 12.9% to 33.1%). The median duration of PRs was 141 days (range, 62 to 299). Of the hematologic toxicities, 14 (23%) and 24 (39%) patients experienced grade 3 or 4 leukopenia and neutropenia, respectively. The toxicities were feasible. Treatment-related death occurred in one patient who suffered hypovolemic shock induced by hematemesis. The median survival time was 10.0 months and the 1-year survival rate was 36.1%. CONCLUSION Combination chemotherapy with concurrent administration of CPT-11 and VP-16 with rhG-CSF support was only modestly effective against metastatic NSCLC, with feasible toxicities of moderate diarrhea and pulmonary toxicity. The results were equivalent to those expected with either cisplatin-based chemotherapy or with CPT-11 alone.
Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic review of 201 patients.
Authors: Smeele L E , Kostense P J , van der Waal I , Snow G B 
Published: February 2017

PURPOSE To evaluate the possible value of chemotherapy in the treatment of craniofacial osteosarcoma (CFOS). DESIGN In a systematic review, data of 201 patients (age, 36.6 +/- 19.0 years [mean +/- SD]) from 20 uncontrolled series on CFOS indexed in Medline and Excerpta Medica between 1974 and 1994 were pooled; 180 patients had undergone surgery. Various chemotherapy regimens had been given to 71 patients. Radiotherapy was used in 69 patients. All patients had data for overall survival, and 182 had data for disease-free survival analysis. Cumulative survival distributions were estimated by the product-limit method, and a multiple regression analysis was performed. RESULTS Patients' overall and disease-free survival rates were significantly improved by treatment with chemotherapy. This was confirmed for patients with complete surgical removal, as well as for those with incomplete removal of tumor. In a proportional hazards model, complete surgical removal and chemotherapy were independent significant factors for overall and disease-free survival. The effect of radiotherapy was insignificant. No prognostic factors could be identified among age groups, sex, and subsites. CONCLUSION Evidence exists that chemotherapy improves survival in CFOS. We advocate the adoption of the chemotherapy protocols used for OS of the long bones for CFOS.
Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia.
Authors: Seiter K , Feldman E J , Halicka H D , Traganos F , Darzynkiewicz Z , Lake D , Ahmed T 
Published: February 2017

PURPOSE To determine the maximal-tolerated dose (MTD) of topotecan with cytarabine in acute leukemia patients, and to evaluate leukemia cell apoptosis in these patients. PATIENTS AND METHODS Fifty-three patients with acute leukemia not responsive to standard therapy were treated at eight dose levels of topotecan (2.5 mg/m2/d to 7.75 mg/m2/d). Topotecan was given as a 30-minute infusion daily with cytarabine 1 g/m2/d, both for 5 days. Using a flow-cytometric technique, the percent apoptotic cells in blood and bone marrow samples was determined, and the cell cycle distribution of the leukemic cells studied. RESULTS Oropharyngeal mucositis was dose-limiting. The MTD of topotecan was 4.75 mg/m2/d for 5 days in high-risk patients and 7.0 mg/m2/d for 5 days in low-risk patients. The mean percent apoptotic cells in the peripheral blood reached a peak of 18.8%, a median of 48 hours following the first dose of topotecan. Patients with higher S-phase fractions, either before treatment or following cytarabine, were more likely to achieve bone marrow aplasia than those with lower S-phase fractions (P = .01 and P < .05, respectively). Clinical responses were seen in four of 39 patients with acute myelogenous leukemia (AML; of whom 32 had received prior high-dose cytarabine), three of six with acute lymphoblastic leukemia (ALL), and one of eight with chronic myelogenous leukemia in blast phase (CML-BP). CONCLUSION The recommended phase II dose of topotecan with intermediate-dose cytarabine is 4.75 mg/m2/d for high-risk patients and 7.0 mg/m2/d for low-risk patients. The percentage of cells in S phase was important in determining response to treatment.
Anthracycline dose in childhood acute lymphoblastic leukemia: issues of early survival versus late cardiotoxicity.
Authors: Sorensen K , Levitt G , Bull C , Chessells J , Sullivan I 
Published: February 2017

PURPOSE Late abnormalities of left ventricular (LV) performance occur in most survivors of childhood acute lymphoblastic leukemia (ALL) treated with moderate anthracycline doses. We studied the prevalence of late cardiotoxicity in patients treated with lower anthracycline doses and related this to survival. PATIENTS AND METHODS Echocardiograms were performed in 50 normal children and 120 relapse-free ALL survivors 6.2 +/- 2.0 years after the end of cumulative daunorubicin doses of 90 mg/m2 (n = 40), 180 mg/m2 (n = 40), or 270 mg/m2 (n = 40) on UKALL X pilot (1982 to 1984) or UKALL X (1985 to 1989) protocols. Age at treatment onset was 4.7 +/- 2.8 years. Cardiac abnormalities were reviewed in light of the UKALL X 5-year disease-free survival rates of 57% (95% confidence interval [CI], 51% to 63%), 61% to 62% (95% CI, 56% to 68%), and 71% (95% CI, 66% to 76%) for the groups that received 90, 180, and 270 mg/m2 of daunorubicin, respectively. RESULTS ALL survivors had reduced LV fractional shortening (FS) compared with normal (32.3% +/- 4.4% v 35.9% +/- 4.2%, P < .005), which was accounted for by increased LV end-systolic stress (49.4 +/- 13.5 v 42.2 +/- 9.1 g/cm2, P < .001), whereas LV contractility independent of loading conditions was normal for the group as a whole. Of 27 patients (23%) with cardiac abnormalities, 25 (21%) had increased end-systolic stress, whereas only two (2%) had reduced contractility. The proportion with cardiac abnormality was similar in the three dose groups. Anthracycline dose, age at treatment, sex, follow-up duration, growth hormone, pubertal status, hemoglobin level, and total WBC count at presentation were not predictive of increased LV end-systolic stress. CONCLUSION There was a reduced incidence and severity of cardiac abnormalities with the lower anthracycline dose protocols (90 to 270 mg/m2) studied compared with previous reports in which subjects had received moderate anthracycline doses (approximately 300 to 550 mg/m2). Cumulative anthracycline dose within the range 90 to 270 mg/m2 did not relate to cardiac abnormalities. This suggests that there may be no safe anthracycline dose to avoid late cardiotoxicity, but reinforces the use of the protocol that affords best survival within the dose range studied.
Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children's Cancer Group.
Authors: Provisor A J , Ettinger L J , Nachman J B , Krailo M D , Makley J T , Yunis E J , Huvos A G , Betcher D L , Baum E S , Kisker C T , Miser J S 
Published: February 2017

PURPOSE The specific aims of this study were to improve event-free survival (EFS) in patients with newly diagnosed nonmetastatic osteosarcoma of an extremity using the histologic response to neoadjuvant chemotherapy to determine postoperative chemotherapy; to evaluate a uniform histologic grading system that measures tumor response; and to identify patient characteristics that might influence EFS and survival. PATIENTS AND METHODS Two hundred sixty-eight patients with nonmetastatic osteosarcoma of the extremity were entered between August 1983 and October 1986. Preoperative chemotherapy consisted of four courses of high-dose methotrexate (MTX) and one course of bleomycin, cyclophosphamide, and dactinomycin (BCD). Histologic response to preoperative chemotherapy was determined by morphometric analysis. Good histologic responders (< 5% residual viable tumor) were treated postoperatively with MTX, BCD, and doxorubicin (DOX); poor histologic responders were treated with BCD, DOX, and cisplatin (CDDP). RESULTS The 8-year EFS and survival rates were 53% and 60%, respectively. Two hundred six patients had their tumors assessed for histologic response: 28% displayed a good histologic response to preoperative chemotherapy. Good histologic responders had an 8-year postoperative EFS rate of 81% and survival rate of 87%; those with a poor histologic response had an 8-year postoperative EFS rate of 46% and survival rate of 52%. A primary tumor site in the proximal humerus or proximal femur and an elevated serum alkaline phosphatase level were associated with an increased risk of an adverse event, whereas the type of surgical procedure was not. CONCLUSION EFS and survival appear to be directly related to histologic response to neoadjuvant chemotherapy.
Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial.
Authors: Ranson M R , Carmichael J , O'Byrne K , Stewart S , Smith D , Howell A 
Published: February 2017

PURPOSE A multicenter phase II study to determine the activity and toxicity of Caelyx (Doxil; Sequus Pharmaceuticals Inc, Menlo Park, CA) in patients with metastatic breast cancer. PATIENTS AND METHODS Seventy-one patients with stage IV breast cancer were treated with Caelyx at doses of 45 to 60 mg/m2 every 3 to 4 weeks for a maximum of six cycles. Twenty-eight patients had received prior chemotherapy with a nonanthracycline regimen. Fifty-two patients had disease at multiple sites. Hepatic and pulmonary disease were the predominant metastatic site in 50 patients. Response was assessable in 64 cases. RESULTS Sixteen patients achieved a partial response and a complete response (overall response rate, 31%; (95% confidence interval, 20% to 43%). Twenty patients (31%) had stable disease on treatment. Neutropenia > or = grade 3 occurred in 10% of cycles (27% of patients) and mucositis > or = grade 3 in 10% of cycles (32% of patients). Significant alopecia was rare and routine prophylactic antiemetics were not required. At doses of 60 mg/m2 every 3 weeks, seven of 13 patients had > or = grade 3 skin toxicity; overall, this toxicity complicated 25% of treatment cycles. The incidence of > or = grade 3 skin toxicity was greatly reduced at doses of 45 mg/m2 every 4 weeks, occurring in five of 32 patients and affecting only 5% of 126 treatment cycles. CONCLUSION Caelyx is an active agent in advanced breast cancer with a safety profile that differs markedly from nonliposomal doxorubicin. A regimen of 45 mg/m2 every 4 weeks was well tolerated in this cohort of women with advanced poor-prognosis breast cancer. The mild myelosuppression seen with this regimen would favor its use in combination chemotherapy.