bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily low-dose cisplatin plus concurrent high-dose thoracic irradiation in locally advanced unresectable non-small-cell lung cancer: results of a phase II Southwest Oncology Group study.
Authors: Hazuka M B , Crowley J J , Bunn P A , O'Rourke M , Braun T J , Livingston R B 
Published: February 2017

PURPOSE This single-arm phase II trial was designed to evaluate the efficacy and toxicity of continuous-course, high-dose thoracic irradiation (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of cisplatin. PATIENTS AND METHODS Sixty-five patients from 21 participating institutions were entered onto the study between April 1989 and May 1991. Protocol therapy consisted of daily intravenous (i.v.) cisplatin (5 mg/m2) plus concurrent continuous-course RT (61 Gy over 6 1/2 weeks) both delivered Monday through Friday each week. After a 3- to 4-week rest period, this was followed by three 28-day cycles of cisplatin at 100 mg/m2 or subsequently 50 mg/m2 administered i.v. on days 1 and 8 of each cycle. RESULTS Sixty-four patients were eligible; the majority had unresectable stage IIIa (36%) or IIIb (55%) NSCLC. The remaining 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is demonstrated by the fact that only five patients (8%) were unable to complete daily cisplatin and RT because of toxicity. Esophagitis (16%), leukopenia (14%), nausea (8%), and vomiting (6%) were the most common severe (grade 3) toxicities. There was only one life-threatening toxicity (grade 4 nausea) and no treatment-related deaths. The objective response rate was 39%, and six patients (9%) achieved a radiographic complete response (CR). The median survival duration for all patients was 14 months, and the 1- and 2-year actuarial survival rates were 56% and 24%, respectively. For stage IIIa patients, the median survival duration and 2-year survival rate were 17 months and 38%, as compared with 10 months and 14% for stage IIIb patients, respectively. CONCLUSION Daily low-dose cisplatin plus concurrent high-dose continuous-course RT is a well-tolerated out-patient regimen. The survival results are encouraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum analogs with RT.
Phase I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors.
Authors: Budman D R , Igwemezie L N , Kaul S , Behr J , Lichtman S , Schulman P , Vinciguerra V , Allen S L , Kolitz J , Hock K 
Published: February 2017

PURPOSE To determine the toxicities, maximum-tolerated dose (MTD), and pharmacology of etoposide phosphate, a water-soluble etoposide derivative, administered as a 5-minute intravenous infusion on a schedule of days 1, 3, and 5 repeated every 21 days. PATIENTS AND METHODS Thirty-six solid tumor patients with a mean age of 63 years, performance status of 0 to 1, WBC count > or = 4,000/microL, and platelet count > or = 100,000/microL, with normal hepatic and renal function were studied. Doses evaluated in etoposide equivalents were 50, 75, 100, 125, 150, 175, and 200 mg/m2/d. Etoposide in plasma and urine and etoposide phosphate in plasma were measured by high-performance liquid chromatography (HPLC). Eleven of 36 patients were treated with concentrated etoposide phosphate at 150 mg/m2/d. RESULTS Grade I/II nausea, vomiting, alopecia, and fatigue were common. Leukopenia (mainly neutropenia) occurred at doses greater than 75 mg/m2, with the nadir occurring between days 15 and 19 posttreatment. All effects were reversible. Hypotension, bronchospasm, and allergic reactions were not observed in the first 25 patients. The MTD due to leukopenia was determined to be between 175 and 200 mg/m2/d. In 11 patients treated with concentrated etoposide phosphate, no local phlebitis was noted, but two patients did develop allergic phenomena. The conversion of etoposide phosphate to etoposide was not saturated in the dosages studied. Etoposide phosphate had peak plasma concentrations at 5 minutes, with a terminal half-life (t1/2) of 7 minutes. Etoposide reached peak concentrations at 7 to 8 minutes, with a t1/2 of 6 to 9 hours. Both etoposide phosphate and etoposide demonstrated dose-related linear increases in maximum plasma concentration (Cmax) and area under the curve (AUC). CONCLUSION Etoposide phosphate displays excellent patient tolerance in conventional dosages when administered as a 5-minute intravenous bolus. The suggested phase II dose is 150 mg/m2 on days 1, 3, and 5. The ability to administer etoposide phosphate as a concentrated, rapid infusion may prove of value both in the outpatient clinic and in high-dose regimens.
Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis after hematopoietic stem-cell transplantation.
Authors: Gordon B , Spadinger A , Hodges E , Ruby E , Stanley R , Coccia P 
Published: February 2017

PURPOSE Oral mucositis following high-dose chemotherapy may result in systemic infection and airway compromise, and the severity of oral mucositis may be dose-limiting. Here we investigate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), which significantly shortens duration of neutropenia after hematopoietic stem-cell transplantation (HSCT) on oral mucositis. PATIENTS AND METHODS Thirteen children undergoing HSCT were prepared with etoposide (VP-16), thiotepa (TT), and total-body irradiation (TBI), and 13 with VP-16, TT, and cyclophosphamide (CPM). Following transplantation, 14 patients received GM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion (six prepared with VP-16, TT, and TBI, and eight prepared with VP-16, TT, and CPM), and 12 patients received no growth factor. RESULTS Mucositis was more severe and persisted longer in patients prepared with the TBI-containing regimen. For this regimen, the duration of severe oral mucositis was shortened by the administration of GM-CSF, although the severity of mucositis was unaffected. No statistically significant effect of GM-CSF could be shown in patients who received VP-16, TT, and CPM. The incidence of positive fungal oral or blood cultures did not appear different whether patients received GM-CSF or not. CONCLUSION For patients undergoing stomatotoxic HSCT regimens, GM-CSF may reduce the duration of oral mucositis, but is unlikely to effect the severity of oral mucositis or risk of airway compromise, and the severity of mucositis is likely to remain dose-limiting.
Pharmacologic-guided trial of sequential methotrexate and thioguanine in children with advanced malignancies.
Authors: Tan C T , Wollner N , Trippett T , Goker E , Tong W P , Kheradpour A , Meyers P A , VanSyckle K M , Guarino L , Elisseyeff Y 
Published: February 2017

PURPOSE Based on in vitro studies that have shown synergistic effects of sequential administration of methotrexate (MTX) and thioguanine (6-TG), we conducted a pharmacologically guided trial of sequential MTX and 6-TG to determine the following: (1) the maximum-tolerated dose (MTD) of 6-TG; (2) the nature of the dose-limiting toxicity; and (3) the modulation effect of MTX on 6-TG given by this sequence and schedule. PATIENTS AND METHODS Thirty-one children with advanced malignancies (acute leukemia, n = 10; lymphoma n = 10; and solid tumors, n = 11) were treated weekly for 3 weeks with a 2-week rest; treatment consisted of a fixed dose of MTX (30 mg/m2 over 24 hours) followed by a 2-hour infusion of 6-TG in escalating doses. RESULTS Measurement of plasma MTX, 6-TG, and mononuclear 5-phosphoribosyl-1-pyrophosphate (PRPP) levels indicates that the desired biochemical modulation and serum levels were achieved. Nonhematologic toxicities were mild and the dose-limiting toxicity was bone marrow depression. A 300-mg/m2 dose of 6-TG with MTX is considered the MTD. Responses were noted in patients with lymphoma. CONCLUSION Encouraging antitumor effects were produced with this regimen in heavily pretreated patients with lymphoma, particularly Hodgkin's disease (HD). The durations of responses were 17, 13+, 12, 9, and 7+ months. A phase II trial of the MTX/6-TG combination is warranted for the treatment of relapsed lymphoma.
Risk of second aerodigestive cancers increases in patients who survive free of small-cell lung cancer for more than 2 years.
Authors: Johnson B E , Linnoila R I , Williams J P , Venzon D J , Okunieff P , Anderson G B , Richardson G E 
Published: February 2017

PURPOSE Patients who survived small-cell lung cancer (SCLC) for more than 2 years were evaluated to determine the frequency and anatomic pattern of redevelopment of small-cell cancer and development of non-small-cell lung cancer (NSCLC) and aerodigestive cancers with the passage of time. PATIENTS AND METHODS From April 1973 through December 1991, 578 patients with previously untreated SCLC were entered onto prospective therapeutic trials at the National Cancer Institute (NCI), Bethesda, MD. Sixty-two (11%) were cancer-free 2 years after initiation of therapy and were assessable for redevelopment of SCLC and development of NSCLC, and aerodigestive cancers. RESULTS Twenty patients redeveloped SCLC 2.0 to 12.2 years after initiation of chemotherapy, of whom two patients were deemed to have a second primary small-cell cancer that involved the aerodigestive tract. Fifteen patients developed 16 cancers in the lung other than SCLC 3.4 to 14.9 years after initiation of therapy. Two developed other aerodigestive cancers that involved the larynx and lip. The risk of a NSCLC and aerodigestive cancer in these patients increased more than sixfold from 2% per patient per year during years 2 to 4 to 12.6% and 14.4%, respectively, after more than 10 years. The cumulative actuarial risk of a second primary NSCLC or aerodigestive cancer at 16 years is 69% and 72%, respectively. CONCLUSION The increasing risk of second aerodigestive cancers with the passage of time is a mounting problem for patients cured of SCLC. Chemoprevention trials for these patients should be considered.
Gonadal function following chemotherapy for Hodgkin's disease: a comparative study of MVPP and a seven-drug hybrid regimen.
Authors: Clark S T , Radford J A , Crowther D , Swindell R , Shalet S M 
Published: February 2017

PURPOSE AND METHODS Gonadal function was assessed in 89 patients after chemotherapy for Hodgkin's disease (HD). Thirty-seven patients had received mechlorethamine, vinblastine, prednisolone, and procarbazine (MVPP) and 52 patients, a hybrid combination of chlorambucil, vinblastine, prednisolone, procarbazine, doxorubicin, vincristine, and etoposide (ChIVPP/EVA). Fifty men (MVPP, n = 21; ChIVPP/EVA, n = 29) with a median age of 26 years (range, 16 to 54) and 39 women (MVPP, n = 16; ChIVPP/EVA, n = 23) with a median age of 30 years (range, 15 to 47) were studied at a median of 30 months (range, 4 to 83) following chemotherapy. RESULTS Semen analysis showed azoospermia in 35 of 37 men, and increased serum follicle-stimulating hormone (FSH) levels in this group confirmed severe germinal epithelial damage. Analysis of pretreatment semen in 28 men showed azoospermia in one, oligospermia in four (sperm count < 20 x 10(6)/mL), and a normal sperm count in the remaining 23. In the women, 26 of 34 (76%) with a regular menstrual cycle before commencing chemotherapy became amenorrheic following treatment. Menses returned in 10 women, who had a median age of 25 years (range, 21 to 34), and there were two pregnancies in this group. In the other 16, with a median age of 36 years (range, 27 to 47), amenorrhea persisted and premature ovarian failure was confirmed by increased serum gonadotrophins and reduced estradiol (E2) concentrations. Of the original eight women in whom menses were maintained following treatment, two subsequently developed amenorrhea and the clinical and biochemical features of an early menopause. In total, 18 of 34 women (53%) required hormone replacement therapy for chemotherapy-induced ovarian failure. CONCLUSION There was no statistically significant difference in the frequency or severity of gonadal dysfunction between MVPP- and ChIVPP/EVA-treated patients. We conclude that both of these chemotherapy schedules cause substantial damage to gonadal function in both sexes.
Multicyclic, dose-intensive chemotherapy supported by sequential reinfusion of hematopoietic progenitors in whole blood.
Authors: Pettengell R , Woll P J , Thatcher N , Dexter T M , Testa N G 
Published: February 2017

PURPOSE To support multicyclic, dose-intensive chemotherapy, we assessed the effects of reinfusing hematopoietic progenitors collected at each cycle in leukapheresis product or whole blood. PATIENTS AND METHODS Twenty-five patients with small-cell lung cancer (SCLC) were treated with six cycles of ifosfamide, carboplatin, and etoposide (ICE) with granulocyte colony-stimulating factor (G-CSF) 300 micrograms/d subcutaneously (SC) on days 4 to 15. Hematopoietic progenitors collected during each cycle were reinfused on day 3 of the next cycle. Cohort 1 (n = 6) was treated every 3 weeks, with leukapheresis after 2 weeks and cryopreservation of the leukapheresis product. Chemotherapy was given if the WBC count was > or = 3 x 10(9)/L and platelet count > or = 100 x 10(9)/L. Cohort 2 (n = 7) was treated every 2 weeks, with leukapheresis on day 1 of the next cycle and storage of the leukapheresis product at 4 degrees C. Cohort 3 (n = 12) was treated every 2 weeks, with 500 to 750 mL of blood drawn by venesection on day 1 of the next cycle and stored at 4 degrees C. In cohorts 2 and 3, chemotherapy was given if the WBC count was > or = 3 x 10(9)/L and platelet count > or = 30 x 10(9)/L. Blood and leukapheresis products were assayed for hematopoietic progenitors. RESULTS ICE chemotherapy with G-CSF was effective in mobilizing blood progenitors (median, 120-fold). Long-term cultures showed no evidence of stem-cell depletion. The cytotoxic dose-intensity of standard every-4-weeks ICE is 100%. In the first three cycles, it was 134% (median) in cohort 1 and 200% in cohorts 2 and 3 (P < .0001). Toxicity and supportive care requirements were not increased. CONCLUSION The dose-intensity of ICE chemotherapy can be doubled by reinfusing hematopoietic progenitors collected by leukapheresis or venesection and stored at 4 degrees C.
Recombinant human granulocyte-macrophage colony-stimulating factor as an adjunct to conventional-dose ifosfamide-based chemotherapy for patients with advanced or relapsed germ cell tumors: a randomized trial.
Authors: Bajorin D F , Nichols C R , Schmoll H J , Kantoff P W , Bokemeyer C , Demetri G D , Einhorn L H , Bosl G J 
Published: February 2017

PURPOSE Ifosfamide-containing therapy with cisplatin plus either etoposide (VIP) or vinblastine (VeIP) can cure of patients with relapsed germ cell tumors (GCTs), but results in substantial myelotoxicity. This study sought to assess the impact of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the severity of neutropenia and incidence of infectious complications in patients who receive ifosfamide-based chemotherapy for GCT. PATIENTS AND METHODS One hundred and four assessable GCT patients from 20 centers were randomized to receive rhGM-CSF with either cycles 1 and 2 or cycles 3 and 4 of chemotherapy. Standard doses of VIP or VeIP were used. Efficacy data were analyzed using a parallel design for cycles 1 and 2 before the crossover. RESULTS Fewer clinically relevant infections occurred in rhGM-CSF patients (13 of 55, 24%) versus observation patients (22 of 49, 45%) in cycle 1 (P = .01). Decreases were observed in infections during neutropenia (22% v 43%, P = .03), infections requiring intravenous antibiotics (20% v 43%, P = .01), and any infection irrespective of severity (29% v 55%, P = .01) in cycle 1. However, there were no significant differences among the treatment arms in cycle 2 in the proportion of clinically relevant infections (P = .23), infections associated with neutropenia (P = .11), infections requiring antibiotics (P = .22), or any infection (P = .65). rhGM-CSF was discontinued in 14% of cycles because of toxicity related to the growth factor. CONCLUSION rhGM-CSF reduced the incidence of infections in the first cycle of chemotherapy, but no benefit beyond the initial chemotherapy cycle was evident. Based on the limited clinical impact and the high incidence of rhGM-CSF-related toxicity that required growth factor discontinuation, the routine administration of rhGM-CSF to prevent neutropenia and infection after ifosfamide-based chemotherapy for GCT patients is not recommended.
Geographic, age, and racial variation in the treatment of local/regional carcinoma of the prostate.
Authors: Harlan L , Brawley O , Pommerenke F , Wali P , Kramer B 
Published: February 2017

PURPOSE Prostate cancer is one of the most common cancers in men. Incidence rates increase with age and are substantially higher in black men than white men. This study examines the variations in the use of radical prostatectomy and radiation by geographic area, age, and race. MATERIALS AND METHODS Data from the National Cancer Institute's Surveillance, Epidemiology, and End-Results Program (SEER) were used to examine treatment differences. Current treatments generally consist of prostatectomy, radiation, or careful observation for clinically localized or regional disease. RESULTS The age-adjusted proportion of men, age 50 and older, who received radical prostatectomy increased sharply between 1984 and 1991, from 11.0% to 32.3% among men with local/regional disease. The choice of treatment varied widely by geographic regions. In 1991, the proportion that received prostatectomy was highest in Utah (47.8%) and lowest in Connecticut (22.5%) among men with localized and regional disease. The increase in radical prostatectomy was not limited to younger men. Although the rates increased for blacks, black men had lower age-adjusted rates of prostatectomy than whites in all years of the study. CONCLUSION The SEER data show a clear trend toward more aggressive treatment, especially prostatectomy. However, the proportion of black men who received prostatectomy was substantially lower than that of white men and this disparity does not appear to be changing.
Incidence of human immunodeficiency virus-related and nonrelated malignancies in a large cohort of homosexual men.
Authors: Lyter D W , Bryant J , Thackeray R , Rinaldo C R , Kingsley L A 
Published: February 2017

PURPOSE To determine if the rates of malignancies other than Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) are increased in human immunodeficiency virus (HIV)-infected homosexual men. SUBJECTS AND METHODS From 1984 through 1993, 1,199 homosexual men were studied in the Pittsburgh component of the Multicenter AIDS Cohort Study (MACS), an examination of the natural history of HIV infection. The cohort consisted of 769 HIV-seronegative (SN) participants and 430 seropositive (SP) members who were either seroprevalent at the time of enrollment or who seroconverted during the study. Cancer incidence data were collected through semiannual visits, phone interviews, medical records, and death certificates. Five thousand seven hundred eight person-years and 2,344 person-years were contributed to the study by the SN and SP men, respectively. RESULTS In addition to 44 cases of KS, 13 NHLs, and 3 CNS lymphomas (CNSLs), 27 other malignancies occurred (three nonmelanoma skin cancers and eight other malignancies in the SP group, eight nonmelanoma skin cancers, and eight other malignancies in the SN group). Age-adjusted rates were calculated for both groups and compared with each other and with rates for the general male population in Pennsylvania. There were no differences between the SN group and the general population. Among the SP group, the combined frequency of all cancers other than KS, NHL, CNSL, and nonmelanoma skin cancers was statistically significantly increased in comparison to both the SN group and the general population. This increase was secondary to an unusually increased frequency of both seminoma and Hodgkin's disease. CONCLUSION These findings support the hypothesis that the incidences of cancers other than KS and lymphoma are moderately increased in the setting of HIV infection and immunosuppression.
CD30 (Ki-1)-positive anaplastic large-cell lymphomas in 13 patients with and 27 patients without human immunodeficiency virus infection: the first comparative clinicopathologic study from a single institution that also includes 80 patients with other human immunodeficiency virus-related systemic lymphomas.
Authors: Tirelli U , Vaccher E , Zagonel V , Talamini R , Bernardi D , Tavio M , Gloghini A , Merola M C , Monfardini S , Carbone A 
Published: February 2017

PURPOSE CD30 (Ki-1)-positive anaplastic large-cell lymphoma (Ki-1 ALCL) rarely has been described in patients with human immunodeficiency virus (HIV) infection. The purpose of this study was to characterize further the clinicopathologic features of Ki-1 ALCL in patients with HIV infection and, for the first time, to make a comparison with Ki-1 ALCL in patients without HIV infection. PATIENTS AND METHODS From September 1987 to April 1993, 93 patients with HIV infection and systemic non-Hodgkin's lymphoma (NHL) were treated at the Cancer Center of Aviano, Italy; in 13 (14%), the diagnosis was of Ki-1 ALCL subtype. This group of patients was compared with the remaining 80 patients who had other HIV-related NHL and with another group of 27 patients with Ki-1 ALCL who were without a diagnosis of HIV infection. RESULTS There was no case of a T-cell phenotype in the 13 HIV-positive Ki-1 ALCL patients, whereas there was such a phenotype in six of 27 (22%) HIV-negative Ki-1 ALCL patients. In regard to the general characteristics of the two groups with Ki-1 ALCL, more patients with stage IV, two or more extranodal sites at presentation, treatment-related leukopenia, and opportunistic infections as the cause of death were observed in the HIV-positive Ki-1 ALCL group. When these variables were compared with those of the other HIV-related NHL group, such differences were not present. CONCLUSION Ki-1 ALCL is not a rare clinicopathologic entity among NHL in patients with HIV infection. The differences observed within the two Ki-1 ALCL groups of patients may be because of factors related to the HIV infection alone.
Tumor angiogenesis as a predictor of recurrence in gastric carcinoma.
Authors: Maeda K , Chung Y S , Takatsuka S , Ogawa Y , Sawada T , Yamashita Y , Onoda N , Kato Y , Nitta A , Arimoto Y 
Published: February 2017

PURPOSE We investigated the correlation between tumor angiogenic activity and progression of gastric carcinoma using immunohistochemical staining with antifactor VIII-related antigen (F-VIII RAg) antibody. MATERIALS AND METHODS One hundred twenty-four specimens resected from patients with gastric carcinoma were investigated by staining with a monoclonal antibody against F-VIII RAg. Correlations between the microvessel count (the mean number of microvessels in the five areas of highest vascular density at 200 times magnification), various clinicopathologic factors, and prognosis were studied. RESULTS The microvessel count increased with histologic stage. The microvessel count was significantly higher in patients with lymph node metastases than in those without such metastases. Moreover, in patients with a high microvessel count (> or = 16), prognosis was significantly poorer than in those with low count (< 16). Multivariate analysis indicated that the microvessel count is an independent prognostic factor in patients with gastric cancer. According to the mode of recurrence, the frequency of hepatic metastases was significantly increased in patients with a high count. CONCLUSION Microvessel count may be a good prognostic indicator and may be useful as a predictor for the mode of recurrence in patients with gastric carcinoma.