bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of Texas M.D. Anderson Cancer Center experience.
Authors: Diamandidou E , Buzdar A U , Smith T L , Frye D , Witjaksono M , Hortobagyi G N 
Published: February 2017

PURPOSE Adjuvant chemotherapy for breast cancer has been the routine practice in the past decade. A number of studies have observed an increased incidence of treatment-related leukemias following chemotherapy with alkylating agents and/or topoisomerase II inhibitors. We evaluated the incidence of treatment-related leukemias in breast cancer patients treated in four adjuvant and two neoadjuvant chemotherapy trials at The University of Texas M.D. Anderson Cancer Center. PATIENTS AND METHODS Between 1974 and 1989, 1,474 patients with stage II or III breast cancer were treated in six prospective trials of adjuvant (n = 4) or neoadjuvant (n = 2) chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (CTX) (FAC) with or without other drugs. The median observation time was 97 months. In 1,107 patients, FAC chemotherapy was given postoperatively; 367 patients received induction chemotherapy, as well as postoperative chemotherapy. Eight hundred ten patients had surgery followed by radiotherapy and chemotherapy; 664 patients had surgery and chemotherapy only. Patients in two adjuvant and one neoadjuvant study received higher cumulative doses of CTX compared with those in the other studies. RESULTS Fourteen cases of leukemia were observed. Twelve of these patients had received radiotherapy and chemotherapy, and two had received chemotherapy only. Six of the reported patients with leukemia were treated with a cumulative CTX dose of greater than 6 g/ m2. Five of these patients had received both radiotherapy and chemotherapy. The median latency period in the 14 patients was 66 months (range, 22 to 113). Six of 10 patients with adequate cytogenetic analyses had abnormalities that involved chromosomes 5 and/or 7. The rest of the patients had nonspecific cytogenetic abnormalities or lacked cytogenetic information. The 10-year estimated leukemia rate was 1.5% (95% confidence interval [CI], 0.7% to 2.9%) for all patients treated, 2.5% (95% CI, 1.0% to 5.1%) for the radiotherapy-plus-chemotherapy group, and 0.5% (95% CI, 0.1% to 2.4%) for the chemotherapy-only group; this difference was statistically significant (P = .01). The 10-year estimated leukemia risk for the higher-dose (> 6 g/m2) CTX group was 2% (95% CI, 0.5% to 5.0%) compared with 1.3% (95% CI, 0.4% to 3.0%) for the lower-dose group, a difference that was not statistically significant (P = .53). CONCLUSION These data illustrate that patients treated with adjuvant FAC chemotherapy plus radiotherapy have a slightly increased risk of leukemia. This information needs to be considered in the treatment plans for patients with breast cancer. However, for most patients, the benefits of adjuvant therapy exceed the risk of treatment-related leukemia.
Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer.
Authors: Crawford J , O'Rourke M , Schiller J H , Spiridonidis C H , Yanovich S , Ozer H , Langleben A , Hutchins L , Koletsky A , Clamon G , Burman S , White R , Hohneker J , Spiridonitis C H 
Published: February 2017

PURPOSE This prospective randomized trial was performed to compare the effectiveness of intravenous vinorelbine tartrate with intravenous fluorouracil and leucovorin (5-FU/LV) on the primary end points of survival, quality of life (QOL), and relief of cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). Secondary end points included tumor response rates and time to treatment failure. In addition, the safety of both treatment regimens was evaluated in this multicenter study. PATIENTS AND METHODS Two hundred sixteen patients with stage IV NSCLC were enrolled onto this study from 18 centers. Vinorelbine was administered at a dose of 30 mg/m2/wk. 5-FU/LV was administered at a dose of 425 mg/m2 and 20 mg/m2, respectively, for 5 consecutive days every 4 weeks. Patients with progressive disease or toxicity were removed from study while responding and stable patients were continued on therapy. RESULTS The median survival time of patients who received vinorelbine was 30 weeks, with 25% of patients alive at 1 year, compared with a median survival time of 22 weeks and 16% of patients alive at 1 year for those treated with 5-FU/LV (P = .03, log-rank test). This improvement in survival was associated with a higher objective response rate (12% v 3%) and time to treatment failure (10 weeks v 8 weeks) for vinorelbine versus 5-FU/LV. The dose-limiting toxicity of vinorelbine was granulocytopenia, with 54% of patients experiencing grade 3/4 granulocytopenia. Nonhematologic toxicity of vinorelbine was generally grade 1 or 2. The most common grade 3 toxicities were related to injection-site reactions. CONCLUSION This trial confirms the efficacy of vinorelbine in patients with advanced NSCLC. The clinical activity and relatively favorable toxicity profile of this agent make it a reasonable and useful treatment option in the management of patients with this disease.
Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas.
Authors: Kuttesch J F , Wexler L H , Marcus R B , Fairclough D , Weaver-McClure L , White M , Mao L , Delaney T F , Pratt C B , Horowitz M E , Kun L E 
Published: February 2017

BACKGROUND An excess risk of second malignancies has been reported in survivors of Ewing's sarcoma. We examined a multiinstitutional data base to reevaluate the risk among survivors of Ewing's sarcoma and to identify possible causal factors. METHODS Information was derived from a data base that included 266 survivors of Ewing's sarcoma. Cumulative incidence rates of second malignancies were calculated. Contributions of clinical features, type and dose of chemotherapy, and cumulative radiation dose to the risk of second malignancies were evaluated. RESULTS After a median follow-up duration of 9.5 years (range, 3.0 to 30), 16 patients have developed second malignancies, which included 10 sarcomas (five osteosarcomas, three fibrosarcomas, and two malignant fibrous histiocytomas) and six other malignancies (acute myeloblastic leukemia, acute lymphoblastic leukemia, meningioma, bronchioalveolar carcinoma, basal cell carcinoma, and carcinoma-in-situ of the cervix). The median latency to the diagnosis of the second malignancy was 7.6 years (range, 3.5 to 25.7). The estimated cumulative incidence rates at 20 years for any second malignancy and for secondary sarcoma were 9.2% (SD = 2.7%) and 6.5% (SD = 2.4%), respectively. The cumulative incidence rate of secondary sarcoma was radiation dose-dependent (P = .002). No secondary sarcomas developed among patients who had received less than 48 Gy, while the absolute risk of secondary sarcoma was 130 cases per 10,000 person-years of observation among patients who had received > or = 60 Gy. CONCLUSION The overall risk of second malignancies after Ewing's sarcomas is similar to that associated with treatment for other childhood cancers. The radiation dose-dependency of secondary sarcomas justifies modification in therapy to reduce radiation doses.
Prostate-specific antigen nadir: the optimum level after irradiation for prostate cancer.
Authors: Critz F A , Levinson A K , Williams W H , Holladay D A 
Published: February 2017

PURPOSE The prostate-specific antigen (PSA) nadir that reflects potential cure of prostate cancer by irradiation has not been established. This report attempts to demonstrate the PSA nadir goal for radiotherapy. MATERIALS AND METHODS From January 1984 through April 1994, 536 stage T1T2NO prostate cancer patients were treated with radioactive iodine 125 (125I) prostate implants followed by external-beam radiation. All were staged node-negative: 68% by pelvic node dissection and the remainder by computed tomographic (CT) scan. The mean pretreatment PSA level was 12.4 ng/mL (median, 8.4 ng/mL; range, 0.3 to 188 ng/mL). The median follow-up duration is 40 months (range, 12 to 138). An increasing posttreatment PSA level defined recurrence. RESULTS Patients who achieved a PSA nadir < or = 0.5 ng/mL had a 95% (+/- 4%) 5-year and an 84% (+/- 12%) 10-year disease-free survival rate, compared with a 5-year disease-free survival rate of 29% (+/- 30%) for those who reached a nadir of 0.6 to 1.0 ng/mL (P = .0001). All patients with a nadir greater than 1.0 ng/mL ultimately failed. Eighty percent of all 536 patients are projected to achieve a nadir < or = 0.5 ng/mL and 90% of patients who achieve this PSA level do so within 48 months of treatment (median, 18 months). Compared with pretreatment PSA level and histologic grade, the PSA nadir is the most significant factor associated with disease-free survival. CONCLUSION For most patients to be successfully treated for prostate cancer with radiotherapy, at least with this combination technique, the PSA nadir should become undetectable (< or = 0.5 ng/mL), similar to that after radical prostatectomy. A PSA nadir of < or = 0.5 ng/mL after radiotherapy for prostate cancer may be used as a reasonable indicator of 10-year disease-free survival.
Complications of venous access ports in 132 patients with disseminated testicular cancer treated with polychemotherapy.
Authors: Lemmers N W , Gels M E , Sleijfer D T , Plukker J T , van der Graaf W T , de Langen Z J , Droste J H , Koops H S , Hoekstra H J 
Published: February 2017

PURPOSE Venous access ports (VAPs) can be used to administer polychemotherapy to patients with malignancies. The purpose of this study was to evaluate perioperative and late complications related to VAP implantations and to analyze factors that may predict the development of complications. PATIENTS AND METHODS During the period 1983 to 1994, 135 VAPs were implanted in 132 patients with disseminated testicular tumors. In a retrospective study, the perioperative and late complications were recorded in this homogeneous patient group. Multivariate analysis was performed to detect factors that may predict the development of complications. RESULTS The median age of the patients was 28 years (range, 16 to 55). Perioperative complications were recorded in five patients (3.7%): pneumothorax in two (1.5%), blood loss in two (1.5%), and mediastinal bleeding in one (0.7%). The ports remained in situ for a total of 55,247 days (median, 413; range, 7 to 1,607). In 31 patients (23%), 42 late complications developed (31%): system obstruction in 13 (9.6%), thrombosis in 11 (8.1%), infection in six (4.4%), catheter defect in six (4.4%), extravasation in four (3.0%), and local skin necrosis in two (1.5%). Late complications were significantly more common in patients who had received chemotherapy before VAP implantation (P < .001). Univariate analysis showed that there were significantly more complications after VAP implantation under local anesthesia than under general anesthesia (P < .05). CONCLUSION Polychemotherapy could be administered in an adequate manner using a VAP. Complications occurred in 26.7% of a homogeneous group of patients who received a VAP implantation for polychemotherapy for disseminated testicular cancer. Chemotherapy treatment before VAP implantation was the only independent risk factor for late complications.
Low cholesterol and cancer.
Authors: Kritz H , Zielinski C , Sinzinger H 
Published: February 2017

PURPOSE The relation between plasma cholesterol (CH) concentration and mortality is complex. The plasma CH concentration correlates positively with mortality from coronary heart disease, but some studies have shown a negative relation with death from cancer. If these two relations reflect causal mechanisms that are reversible by changing the plasma CH concentration, the benefits of lipid reduction for heart disease might be offset by an increased mortality from cancer. Different aspects between lipid metabolism and cancer, as well as new insights into this interesting field, are discussed. METHODS The literature was searched using MedLine through 1966 and January 1996. RESULTS There is no evidence from the data available at present that the association between low CH and a higher risk of cancer is causal. CONCLUSION This issue should not affect the advice on health matters offered by doctors, especially to patients with other risk factors for cardiovascular disease. The possibility that hypercholesterolemia (HC) drugs can induce a reduction of tumor-cell growth makes them potentially useful as an adjuvant to chemotherapy and ultimately increases the probabilities in the prevention and treatment of cancer.
Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase.
Authors: Baker S D , Khor S P , Adjei A A , Doucette M , Spector T , Donehower R C , Grochow L B , Sartorius S E , Noe D A , Hohneker J A , Rowinsky E K 
Published: February 2017

PURPOSE To study the absolute bioavailability and pharmacokinetics of an oral solution of fluorouracil (5-FU) in patients treated with 776C85, an oral inactivator of dihydropyrimidine dehydrogenase (DPD), and to evaluate the feasibility of administering oral 5-FU and 776C85 on a multiple-daily dosing schedule. PATIENTS AND METHODS Twelve patients with refractory solid tumors were enrolled onto this three-period study. In periods 1 and 2, patients were randomly assigned to treatment with 5-FU 10 mg/m2 on day 2 given by either the oral or intravenous (IV) route with oral 776C85 3.7 mg/m2/d on days 1 and 2. In period 3, patients received escalating doses of 5-FU (10 to 25 mg/ m2/d) orally for 5 days (days 2 to 6) with 776C85 3.7 mg/m2/d orally (days 1 to 7) every 4 weeks. Pharmaco-kinetic studies were performed in periods 1 and 2, and after the fifth oral dose of 5-FU in period 3. RESULTS Twelve patients completed the bioavailability and pharmacokinetic studies. Following oral 5-FU 10 mg/m2, the bioavailability was 122% +/- 40% (mean +/- SD), the terminal half-life (t1/2 beta) was 4.5 +/- 1.6 hours, the apparent volume of distribution (V beta) was 21.4 +/- 5.9 L/ m2, and the systemic clearance (Clsys) was 57.6 +/- 16.4 mL/min/m2. A correlation was observed between oral 5-FU systemic clearance and calculated creatinine clearance (r = .74; P = .009). Multiple-daily dosing did not appear to affect the pharmacokinetics of oral 5-FU. Neutropenia was the principal toxicity of oral 5-FU and 776C85, precluding escalation of oral 5-FU to doses greater than 25 mg/m2/d for 5 days every 4 weeks with 776C85. CONCLUSION The oral DPD inactivator 776C85 enables oral administration of 5-FU and may alter conventional 5-FU administration practices.
Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer.
Authors: Venturini M , Michelotti A , Del Mastro L , Gallo L , Carnino F , Garrone O , Tibaldi C , Molea N , Bellina R C , Pronzato P , Cyrus P , Vinke J , Testore F , Guelfi M , Lionetto R , Bruzzi P , Conte P F , Rosso R 
Published: February 2017

PURPOSE Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane: doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity. PATIENTS AND METHODS One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to < or = 45%, or a decrease from baseline resting LVEF of > or = 20 EF units. RESULTS One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxone arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms. CONCLUSION Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.
Prospective comparison of the sclerosing agents doxycycline and bleomycin for the primary management of malignant pericardial effusion and cardiac tamponade.
Authors: Liu G , Crump M , Goss P E , Dancey J , Shepherd F A 
Published: February 2017

PURPOSE To compare the clinical efficacy and toxicity of doxycycline and bleomycin as sclerosing agents in the primary management of malignant pericardial effusion (MPE). METHODS Twenty-seven consecutive adult patients referred to a tertiary-care institution for the management of cardiac tamponade and malignancy underwent pericardial drainage through a percutaneously placed pigtail catheter. They were then alternately assigned to undergo bleomycin or doxycycline pericardial sclerosis. RESULTS There were 13 men and 14 women, with a median age of 59 years. They mainly had lung (70%) and breast cancers (11%), and all had clinical and echocardiographic evidence of cardiac tamponade. Although all patients had successfully placed catheters, six were inadvertently dislodged before sclerosis; 11 underwent bleomycin sclerosis and 10 doxycycline sclerosis. Twenty patients (one early death) were assessable. One patient in each group failed to respond to sclerosis with the initial agent, but both were sclerosed successfully with the other agent. Sclerosis was achieved with a median of two instillations for each agent and total median doses of bleomycin 20 mg and doxycycline 1,250 mg. Seventy percent of doxycycline patients developed significant retrosternal pain, compared with no bleomycin patients (P = .04). Doxycycline patients required a median of 3.5 more days of hospitalization (8.5 v 5) and 2 more days of pericardial catheterization (7 v 5) compared with bleomycin patients. Tamponade recurred in one bleomycin patient at 253 days, and in no doxycycline patient. CONCLUSION Although bleomycin and doxycycline are equally effective sclerosing agents, bleomycin is associated with significantly less morbidity and should be the first-line chemical sclerosing agent for malignant pericardial effusions.
nm23 in ovarian cancer: correlation with clinical outcome and other clinicopathologic and biochemical prognostic parameters.
Authors: Scambia G , Ferrandina G , Marone M , Benedetti Panici P , Giannitelli C , Piantelli M , Leone A , Mancuso S 
Published: February 2017

PURPOSE The aim of the study was to define the prognostic role of the metastasis suppressor gene, nm23, in 106 primary ovarian cancer patients. PATIENTS AND METHODS Northern and Western blotting analysis of nm23-H1 and nm23-H2 expression were performed in a subset of ovarian tumors. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens from 106 primary ovarian carcinomas by the antihuman nm23 monoclonal antibody. RESULTS Northern and Western blotting analysis demonstrated a direct association between nm23-H1 and nm23-H2 levels. Moreover, an overall concordance of 86.7% between Northern blotting and immunohistochemical data was observed. Sixty-six specimens (68%) showed a positive nm23-H1 immunoreaction. The percentage of nm23-H1 positivity was higher in lymph node-negative (70%) than in lymph node-positive cases (44%) (P = .049). Moreover, the percentage of complete/partial responses to chemotherapy was higher in nm23-H1-positive (69%) than in nm23-H1-negative (44%) patients (P = .03). The percentage of epidermal growth factor receptor (EGFR) positive cases was lower in nm23-H1-positive (44%) than in nm23-H1-negative immunostained (72%) samples (P = .012). Lower ras/p21 levels (median, 1.77 absorbance units) were found in nm23-H1-positive than in nm23-H1-negative samples (median, 2.63 absorbance units) (P = .03). The 6-year progression-free survival (PFS) rate of nm23-H1-positive cases was 50% (95% confidence interval [CI], 33 to 67) versus 12% (95% CI, -2 to 26) for nm23-H1-negative patients (P = .0056). In multivariate analysis, only stage, ascites, and nm23-H1 content retained independent prognostic roles. CONCLUSION The assessment of nm23 content may provide useful information for prognostic characterization of ovarian cancer patients.
Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy.
Authors: Pujade-Lauraine E , Guastalla J P , Colombo N , Devillier P , François E , Fumoleau P , Monnier A , Nooy M , Mignot L , Bugat R , Marques C , Mousseau M , Netter G , Maloisel F , Larbaoui S , Brandely M 
Published: February 2017

PURPOSE The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy. PATIENTS AND METHODS One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy. RESULTS Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted. CONCLUSION These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.