bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy.
Authors: Weaver C H , Appelbaum F R , Petersen F B , Clift R , Singer J , Press O , Bensinger W , Bianco J , Martin P , Anasetti C 
Published: February 2017

PURPOSE To evaluate high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in patients with lymphoid malignancy who had received prior radiation therapy. PATIENTS AND METHODS Fifty-seven patients with non-Hodgkin's lymphoma (NHL; n = 23), Hodgkin's disease (HD, n = 32), or acute lymphoblastic leukemia (ALL; n = 2) with a history of previous radiation therapy were treated with cyclophosphamide (Cy; 7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2) (CBV) followed by ABMT. RESULTS The projected 2-year probabilities of survival, event-free survival (EFS), and relapse were .31, .24, and .76, respectively. For patients with intermediate- and high-grade lymphoma and HD the probabilities were .27, .10, and .14 for EFS and .57, .90, and .77 for relapse. The probability of nonrelapse mortality in the first 100 days post-ABMT was 33%. Idiopathic pneumonia syndrome (IPS) was observed in no patients who received carmustine 300 mg/m2 and 23% of patients who received carmustine 600 mg/m2 (P = .05). Eight-three percent of patients who received mediastinal radiation therapy less than 3 months before transplant developed IPS, compared with 13% who received radiation therapy more than 3 months before transplant (P = .001). CONCLUSION ABMT following high-dose CBV resulted in long-term disease-free survival in 25% of patients with lymphoid malignancies who had previously received dose-limiting radiation therapy. Fatal IPS and a high relapse rate were major factors limiting successful outcome following ABMT. The morbidity and mortality rates associated with the administration of carmustine 600 mg/m2 were prohibitively high, especially in patients who received mediastinal radiation immediately before ABMT, and were not associated with a decrease in post-ABMT relapse.
OVX1 radioimmunoassay complements CA-125 for predicting the presence of residual ovarian carcinoma at second-look surgical surveillance procedures.
Authors: Xu F J , Yu Y H , Daly L , DeSombre K , Anselmino L , Hass G M , Berchuck A , Soper J T , Clarke-Pearson D L , Boyer C 
Published: February 2017

PURPOSE At second-look surgical surveillance procedures, normal CA-125 levels can be associated with persistent disease in 50% to 60% of patients. A novel radioimmunoassay (RIA) has been evaluated for the ability to identify patients with persistent disease who have normal levels of CA-125. MATERIALS AND METHODS The OVX1 double-determinant assay used a murine monoclonal antibody to detect an epitope on a high-molecular weight mucin-like glycoprotein. RESULTS Apparently healthy individuals had serum OVX1 levels of 2.23 +/- 2.48 U/mL (mean +/- SD). Elevated serum OVX1 levels (> 7.2 U/mL) were found in 5% of 184 normal individuals and in 70% of 93 epithelial ovarian cancer patients with clinically evident disease. Among sera from these ovarian cancer patients, OVX1 was elevated in 68% of 76 samples with CA-125 levels more than 35 U/mL and in 76% of 17 samples with CA-125 levels less than 35 U/mL. In serum samples obtained at the time of positive second-look laparotomy, 59% of 41 patients with CA-125 levels less than 35 U/mL had elevated OVX1 antigen levels, whereas 41% of 22 patients with CA-125 levels more than 35 U/mL had elevated serum OVX1 levels. In patients with negative second-look laparotomies, false-positive results were eliminated by increasing the threshold of OVX1 to 10.5 U/mL. At this level, 32% of 41 patients with positive second-look operations had an elevated OVX1 level, despite a normal CA-125 level. When used in combination, CA-125 (> 35 U/mL) and OVX1 (> 10.5 U/mL) detected persistent disease in 56% of 63 patients with positive surveillance procedures, compared with 35% when CA-125 was used alone (P < .05). CONCLUSION An elevated OVX1 level can alert oncologists to the possibility that ovarian cancer has persisted, despite the return of CA-125 to a normal range.
Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial.
Authors: Stehman F B , Bundy B N , Thomas G , Keys H M , d'Ablaing G , Fowler W C , Mortel R , Creasman W T 
Published: February 2017

PURPOSE Long-term follow-up data of a randomized trial that compared hydroxyurea and the hypoxic-cell radiosensitizer to misonidazole as adjuncts to standard radiation therapy in locally advanced carcinoma of the cervix are reported. PATIENTS AND METHODS Three hundred eight women were entered, and all 294 eligible patients are assessable as randomized. Eighty-one percent of patients have been monitored for 5 years or to death. RESULTS There was an advantage for hydroxyurea in progression-free interval and survival (P = .05 and P = .066, respectively). There was no significant difference in the distribution of sites of failure between the regimens. For the 39% of patients with stages III to IVA disease, the advantage in progression-free interval for hydroxyurea was significant (47.8% v 33.6%). More leukopenia occurred on the hydroxyurea regimen than on the misonidazole regimen. CONCLUSION In summary, these data provide stronger evidence than our previous analysis that hydroxyurea is superior to misonidazole as an adjunct to radiation therapy. For patients with locally advanced carcinoma of the cervix, hydroxyurea continues to be the adjunct of choice with radiation.
EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma.
Authors: Wilson W H , Bryant G , Bates S , Fojo A , Wittes R E , Steinberg S M , Kohler D R , Jaffe E S , Herdt J , Cheson B D 
Published: February 2017

PURPOSE Based on in vitro evidence that tumor cells are less resistant to prolonged exposure to low concentrations of the natural product class, compared with brief higher concentration exposure, we developed a chemotherapy regimen (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone [EPOCH]) in which the natural products are administered as a continuous infusion. PATIENTS AND METHODS This is a phase II study of etoposide, vincristine, and doxorubicin, administered as a 96-hour continuous infusion, with intravenous (IV) bolus cyclophosphamide and oral prednisone (EPOCH) in 74 consecutive patients who relapsed from or failed to respond to most of the same drugs administered on a bolus schedule. Patients with aggressive lymphomas who achieved a good response after EPOCH were eligible to undergo bone marrow transplantation. RESULTS Patients with intermediate- or high-grade lymphoma comprised 76% of this series and 77% had stage IV disease. Seventy-one percent had previously received all of the drugs contained in the EPOCH regimen and 92% had received at least four of the drugs. Seventy patients were assessable for response, of whom 19 (27%) achieved a complete remission (CR) and 42 (60%) a partial remission (PR). Among 21 patients who had no response to prior chemotherapy, 15 (71%) responded, but only one achieved a CR. Patients who relapsed from an initial CR had a 100% response rate, with 76% CRs. With a median potential follow-up duration of 19 months, there was a 28% probability of being event-free at 1 year. Toxicity was primarily hematologic with neutropenia during 51% of cycles, but only a 17% incidence of febrile neutropenia. Gastrointestinal, neurologic, and cardiac toxicity were minimal. CONCLUSION EPOCH chemotherapy was well tolerated and highly effective in patients who were resistant to or relapsed from the same drugs administered on a bolus schedule, suggesting that continuous infusion of the natural drug component of this regimen is capable of partially reversing drug resistance and reducing toxicity. Dose-intensity (DI) was > or = that achieved in primary treatment regimens for aggressive lymphomas.
Busulfan plus cyclophosphamide followed by autologous blood stem-cell transplantation for patients with acute myeloblastic leukemia in first complete remission: a report from a single institution.
Authors: Sanz M A , de la Rubia J , Sanz G F , Martín G , Martínez J , Jarque I , Sempere A , Gomis F , Senent L , Soler M A 
Published: February 2017

PURPOSE To determine if peripheral-blood stem cells (PBSC) collected during the recovery of standard induction and consolidation chemotherapy in acute myeloblastic leukemia (AML) can be used as a safe tool for autologous transplantation, and to study aspects of the autologous blood stem-cell transplantation (ABSCT) procedure and their results in AML patients in first remission. PATIENTS AND METHODS Twenty-four AML patients in first remission received busulfan (BU; 16 mg/kg) and cyclophosphamide (CY; 200 mg/kg) followed by ABSCT. PBSC were collected by continuous-flow leukaphereses after induction and consolidation courses. RESULTS The median numbers of mononuclear cells (MNCs) and colony-forming unit granulocyte-macrophage (CFU-GM) administered were 6 x 10(8)/kg and 11 x 10(4)/kg, respectively. ABSCT induced engraftment in 22 patients and there were two graft failures. The median times to reach a polymorphonuclear (PMN) leukocyte count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L were 13 and 19 days, respectively. Fatal hepatic veno-occlusive disease (VOD) was observed in two cases. Other toxicities were mild and uncommon. Twelve patients relapsed between 1 and 9 months posttreatment. Actuarial disease-free survival (DFS) and actuarial risk of relapse at 30 months were 35% (95% confidence interval [CI], 25% to 45%) and 60% (95% CI, 50% to 72%), respectively. CONCLUSION These preliminary results show the fast hematopoietic recovery and the low infectious and hemorrhagic morbidity associated with the procedure and strongly suggest that ABSCT may be as effective as autologous bone marrow transplantation (ABMT) in AML. However, further strategies for reducing leukemic relapse must still be investigated.
Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients.
Authors: Rossi R , Gödde A , Kleinebrand A , Riepenhausen M , Boos J , Ritter J , Jürgens H 
Published: February 2017

PURPOSE This study was performed to identify risk factors of ifosfamide-induced renal damage. PATIENTS AND METHODS Renal function was assessed in 120 patients at a minimum of 3 months after completion of chemotherapy including ifosfamide. The cumulative ifosfamide dose ranged from 2 to 95 g/m2 (median, 30 g/m2). Ten patients had undergone unilateral nephrectomy; combination cytostatic treatment included cisplatin in 51 and methotrexate in 57. Sixty-eight patients had received gentamicin treatment. The glomerular filtration rate was estimated using the Schwartz formula. Proximal tubular function was assessed by the percent reabsorptions of glucose and 16 amino acids, the fractional excretion of sodium, and the fractional reabsorption of phosphate. In addition, the serum bicarbonate level was measured. RESULTS Proximal tubular dysfunction--with a predominance of renal amino acid (66.3%) and phosphate loss (38.3%)--was much more frequent than both glomerular impairment and acidosis. Seven patients were identified as having renal Fanconi's syndrome, and generalized tubulopathy was noted in another 15 patients. Ifosfamide-induced nephrotoxicity was dose-dependent, with a weak linear inverse correlation between cumulative ifosfamide dose and fractional phosphate reabsorption. Unilateral nephrectomy proved to be the single most important risk factor (odds ratio for the development of renal Fanconi's syndrome, 11.4), but cisplatin also significantly enhanced ifosfamide-mediated nephrotoxicity. Methotrexate, gentamicin, and patient age at primary diagnosis had no influence on renal function. CONCLUSION Ifosfamide chemotherapy should probably be restricted in patients after unilateral nephrectomy.
Phase I/II and pharmacologic study of long-term continuous infusion etoposide combined with cisplatin in patients with advanced non-small-cell lung cancer.
Authors: Kunitoh H , Watanabe K 
Published: February 2017

PURPOSE The primary objective of this study was to determine the pharmacodynamics of prolonged administration of low-dose etoposide by continuous infusion (CI). We investigated the hypothesis that maintenance of an etoposide concentration of 1 microgram/mL would be cytotoxic in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty patients with advanced NSCLC without prior chemotherapy or radiotherapy were treated with etoposide at 20, 25, or 30 mg/m2/d infused continuously for 14 days (336 hours), following a 10-mg/m2 bolus. They also received cisplatin 30 mg/m2 on chemotherapy days 1, 2, and 3. Plasma concentrations of etoposide were measured by high-performance liquid chromatography at 0, 2, 4, 24, 48, 120, 336, and 342 hours after initiation of CI etoposide. RESULTS The maximum-tolerated dose (MTD) of etoposide was 25 mg/m2/d with leukocytopenia as the dose-limiting toxicity. Plasma concentrations of etoposide at steady-state (Css) showed approximately twofold interpatient variability at each dose level, and were greater than 1 microgram/mL in most patients at higher dose levels. The severity of neutropenia was dependent on performance status (PS), age, and the Css of etoposide. The overall response rate for the 29 assessable cases was 28%. Five of 11 patients with a Css greater than 1.2 micrograms/mL responded to the therapy, whereas only one of 10 patients with a Css less than 1 microgram/mL responded. CONCLUSION With long-term CI of etoposide, a Css greater than 1 or 1.2 micrograms/mL appeared necessary, but not sufficient, to achieve a major response against NSCLC.
First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research.
Authors: Borner M , Bacchi M , Goldhirsch A , Greiner R , Harder F , Castiglione M , Jungi W F , Thürlimann B , Cavalli F , Obrecht J P 
Published: February 2017

PURPOSE We performed a randomized phase III multicenter study to compare systemic treatment versus no treatment after complete excision and radiotherapy for isolated first locoregional recurrence in patients with breast cancer. PATIENTS AND METHODS One hundred sixty-seven good-risk patients with an estrogen receptor (ER+) positive recurrence or, in case of unknown receptor status, a disease-free interval (DFI) of greater than 12 months and < or = three recurrent tumor nodules each < or = 3 cm in diameter were entered onto the study. They were randomized to observation subsequent to local treatment or to receive tamoxifen (TAM) until disease progression. Seventy-nine percent of the patients were postmenopausal. RESULTS The median observation period for the entire study population was 6.3 years. The median disease-free survival (DFS) duration was 26 months for observation and 82 months for TAM patients (P = .007). This was mainly due to the reduction of further local recurrences, whereas the occurrence of early distant metastases was delayed. A multivariate analysis identified DFI and treatment with TAM as significant prognostic factors for DFS. The 5-year overall survival (OS) rates were 76% and 74%, respectively (P = .77). DFI was also a prognostic factor for OS. CONCLUSION Systemic therapy with TAM after isolated locoregional recurrence of breast cancer significantly increased 5-year DFS rates from 36% to 59% compared with observation alone and prolonged median DFS by more than 4.5 years in patients with ER+ tumors or in the case of unknown ER status with a DFI of greater than 12 months and minimal tumor burden. Treatment with TAM currently has no significant impact on OS, but the median survival duration of the study population has not yet been reached.
Randomized 2 x 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients. German Breast Cancer Study Group.
Authors: Schumacher M , Bastert G , Bojar H , Hübner K , Olschewski M , Sauerbrei W , Schmoor C , Beyerle C , Neumann R L , Rauschecker H F 
Published: February 2017

PURPOSE In 1984, the German Breast Cancer Study Group (GBSG) started a multicenter randomized clinical trial to compare the effectiveness of three versus six cycles of 500 mg/m2 cyclophosphamide, 40 mg/m2 methotrexate, and 600 mg/m2 fluorouracil (CMF) on day 1 and 8 starting perioperatively with or without tamoxifen (TAM) (3 x 10 mg/d for 2 years). The aim of the trial was to compare recurrence-free and overall survival between the different treatment modalities. PATIENTS AND METHODS During 5 years, 41 institutions randomized 473 patients (3 x CMF: 145; 3 x CMF + TAM: 93; 6 x CMF 144; 6 x CMF + TAM: 91). Until March 31, 1992, median follow-up time was 56 months with 197 events for disease-free survival and 116 deaths observed. This provides a power of approximately 80% to detect a potential treatment difference corresponding to a relative risk (RR) of 0.67 for recurrence-free survival. Treatment modalities and various patient characteristics were evaluated by means of a multivariate Cox regression analysis. RESULTS No significant difference in recurrence-free survival was observed with respect to hormonal therapy (RR = 0.75 TAM v no TAM; 95% confidence interval [CI], 0.54 to 1.04; P = .08) as well as duration of chemotherapy (RR = 0.90 of 6 x CMF v 3 x CMF; 95% CI, 0.67 to 1.19; P = .45). Similar results were obtained for overall survival. The multivariate analysis revealed a significant prognostic impact of the number of positive lymph nodes and the progesterone receptor level on recurrence-free survival. Compliance with chemotherapy within the range of 85% to 115% of the target dose was achieved in 94% and 78% of the patients randomized to 3 x CMF and 6 x CMF, respectively. Sufficient compliance with TAM was reported for 141 patients (93%). CONCLUSION At this stage of follow-up, six courses of CMF are not superior to three courses with respect to recurrence-free survival.
Treatment of children with clear-cell sarcoma of the kidney: a report from the National Wilms' Tumor Study Group.
Authors: Green D M , Breslow N E , Beckwith J B , Moksness J , Finklestein J Z , D'Angio G J 
Published: February 2017

PURPOSE To evaluate the effect of the sequential addition of doxorubicin (DOX) and cyclophosphamide (CTX) to the combination of vincristine (VCR) and dactinomycin (AMD) on the relapse-free survival of children with clear-cell sarcoma of the kidney (CCSK). PATIENTS AND METHODS We determined the 6-year relapse-free survival rate for patients with CCSK treated on National Wilms' Tumor Study (NWTS)-1, NWTS-2, or NWTS-3 with the combination of VCR and AMD, with or without DOX, and for patients treated on NWTS-3 with the combination of VCR, AMD, and DOX with (regimen J) or without (regimen DD-RT) CTX. RESULTS The 6-year relapse-free survival rate for the eight children with CCSK treated with VCR, AMD, and radiation therapy was 25.0%, compared with 63.5% for the 58 children treated with VCR, AMD, DOX, and radiation therapy (P = .09). The 6-year relapse-free survival rate for children with CCSK treated on regimen DD-RT was 64.6%, compared with 58.2% for those treated on regimen J (P = .79). CONCLUSION We conclude that the addition of DOX to the combination of VCR plus AMD appeared to improve the 6-year relapse-free survival rate of children with CCSK. The addition of CTX in the dose and schedule used in NWTS-3 did not improve the 6-year relapse-free survival rate of children with CCSK. Because 30% of relapses occurred more than 2 years after diagnosis, prolonged follow-up evaluation of patients with CCSK is necessary.
Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination chemotherapy.
Authors: Longo D L , Duffey P L , Jaffe E S , Raffeld M , Hubbard S M , Fisher R I , Wittes R E , DeVita V T , Young R C 
Published: February 2017

PURPOSE To review the efficacy of cyclophosphamide, doxorubicin, etoposide, methotrexate with leucovorin, and prednisone (ProMACE)-based combination chemotherapy programs in the treatment of patients with diffuse small noncleaved-cell non-Burkitt's lymphoma. PATIENTS AND METHODS Thirty-three patients with diffuse small noncleaved-cell non-Burkitt's lymphoma were accrued: eight with localized disease were treated with modified ProMACE-mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus involved-field radiation therapy, and 25 with advanced-stage disease were treated with ProMACE/MOPP flexitherapy (n = 8), ProMACE-MOPP (n = 9), or ProMACE-cytarabine, bleomycin, vincristine, and methotrexate with leucovorin (CytaBOM) (n = 8). The median follow-up duration is 10 years. RESULTS All eight patients with localized disease achieved a complete response, none have relapsed, and one died of intercurrent illness. Among patients with advanced-stage disease, five of eight (63%) flexitherapy-treated patients, six of nine (67%) ProMACE-MOPP-treated patients, and eight of eight (100%) ProMACE-CytaBOM-treated patients achieved a complete response. If the two ProMACE-MOPP-based groups are considered together, disease-free and overall survival rates at 15 years are projected at 61% and 35%, respectively. In contrast, only one patient has relapsed from a ProMACE-CytaBOM-induced complete remission, and overall survival of ProMACE-CytaBOM-treated patients (88%) is significantly higher than that for flexitherapy and ProMACE-MOPP (P2 = .04). CONCLUSION Adult patients with diffuse small non-cleaved-cell non-Burkitt's lymphoma may be effectively treated with regimens that are effective in other aggressive lymphomas (eg, diffuse large-cell lymphoma).
ABVD/MOPP and low-dose involved-field radiotherapy in pediatric Hodgkin's disease: the Stanford experience.
Authors: Hunger S P , Link M P , Donaldson S S 
Published: February 2017

PURPOSE We reported previously that treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and 15 to 25 Gy irradiation was effective in curing children with Hodgkin's disease, but was associated with a 6.5% 10-year risk of development of secondary leukemia. Based on the results of that study, a successor study was designed with the objective to maintain treatment efficacy while decreasing adverse effects, particularly the occurrence of secondary leukemia. PATIENTS AND METHODS Fifty-seven children with a chronologic and/or bone age less than 16 years were enrolled onto this study between May 1982 and October 1990. Treatment consisted of six cycles of combination chemotherapy--three of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and three of MOPP--and low-dose irradiation (15 Gy) of involved fields. Boosts of 10 Gy were given to areas of bulky disease and to those that did not respond completely after two cycles of chemotherapy. RESULTS With a median follow-up duration of 6.7 years, the projected 10-year survival and event-free survival (EFS) rates are 96% (SE 2.5%) and 93% (SE 3.5%) for the entire cohort of 57 patients, and 85% (SE 10%) and 69% (SE 12.8%), respectively, for 13 patients with stage IV disease. No patient has developed a second malignancy. Growth and development have progressed normally. No patients have symptomatic cardiac, pulmonary, or thyroid disease. Subclinical abnormalities of pulmonary function were detected in 32% and chemical hypothyroidism in 16%. CONCLUSION This therapy was highly efficacious in children with Hodgkin's disease without unacceptable toxicity. Future efforts should be directed toward further reducing therapy for favorable early-stage patients and improving treatment efficacy for those with stage IV disease.