bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP.
Authors: Verdonck L F , Dekker A W , de Gast G C , van Kempen M L , Lokhorst H M , Nieuwenhuis H K 
Published: February 2017

PURPOSE We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy. PATIENTS AND METHODS Thirty-one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT. RESULTS Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow-up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity. CONCLUSION ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment.
A prospective study of a new combination chemotherapy regimen in patients older than 70 years with unfavorable non-Hodgkin's lymphoma.
Authors: Tirelli U , Zagonel V , Errante D , Serraino D , Talamini R , De Cicco M , Carbone A , Monfardini S 
Published: February 2017

PURPOSE A prospective trial with a new combination of etoposide, mitoxantrone, and prednimustine (VMP), specifically devised for elderly patients with non-Hodgkin's lymphoma (NHL), was undertaken. PATIENTS AND METHODS Between January 1987 and April 1990, 52 consecutive unselected patients older than 70 years (median age, 75.6 years) with stage I to IV intermediate- and high-grade NHL, or with stage III to IV low-grade malignancy with symptomatic disease received etoposide and prednimustine 80 mg/m2 orally for 5 days and mitoxantrone 8 to 10 mg/m2 day 1 intravenously (IV), every 21 days. Fourteen patients were previously treated. RESULTS Among the 48 assessable patients, the objective response rate was 81%; 46% of the patients achieved a complete response (CR). The overall toxicity seemed to be acceptable, with 15 (7%) episodes of grade 4 leukopenia and 41 (18%) episodes of grade 3, over a total of 226 administered cycles. The median survival was 12 months. The patients who obtained CR have a longer survival than those who did not (34 v 8 months; P less than .001). Fifty-eight percent of patients achieving CR were free from relapse at 24 months; up to 36 months from the start of therapy, 25% were free from relapse. As far as patients affected by diffuse histiocytic lymphoma, 66% of previously untreated patients obtained a CR, and 55% of them were still disease-free at 24 months from the start of therapy. CONCLUSION We conclude that VMP is effective, well tolerated, and feasible on an outpatient basis in an unselected, elderly population affected by unfavorable NHL.
Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.
Authors: Markman M , Hakes T , Reichman B , Lewis J L , Rubin S , Jones W , Almadrones L , Pizzuto F , Hoskins W 
Published: February 2017

PURPOSE There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting. PATIENTS AND METHODS Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities. RESULTS Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program. CONCLUSION Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.
Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.
Authors: Roth B J , Johnson D H , Einhorn L H , Schacter L P , Cherng N C , Cohen H J , Crawford J , Randolph J A , Goodlow J L , Broun G O 
Published: February 2017

PURPOSE The trial was undertaken to determine (1) the relative efficacy/toxicity of two commonly used combination chemotherapy regimens in patients with extensive small-cell lung cancer (SCLC) and (2) whether the rapid alternation of these two regimens could provide superior therapeutic results compared with either regimen alone. PATIENTS AND METHODS In this phase III trial, 437 eligible patients were stratified by performance status (PS) and sex and were randomly assigned to receive either 12 weeks of cisplatin and etoposide (EP); 18 weeks of cyclophosphamide, doxorubicin, and vincristine (CAV); or 18 weeks of alternation of these two regimens (CAV/EP). RESULTS There were no significant differences in treatment outcome for EP, CAV, or CAV/EP in terms of response rate (61%, 51%, 59%, respectively), complete response rate (10%, 7%, 7%, respectively), or median survival (8.6 months, 8.3 months, 8.1 months, respectively), with a non-statistically significant trend toward a longer median time to progression with alternating therapy (4.3 months, 4.0 months, 5.2 months, respectively). Crossover second-line chemotherapy given at progression produced low response rates and short survival, regardless of the regimen used. Myelosuppression was the dose-limiting toxicity for all patients, although the pattern and severity differed among the treatment arms. CONCLUSIONS The combination regimens EP and CAV can be considered equivalently effective induction therapies in extensive SCLC, and these two regimens are, to some degree, crossresistant. Alternating therapy provides no therapeutic advantage compared with the use of either of these regimens alone and should not be considered as standard treatment in this clinical setting.
Factors influencing cosmetic outcome and complication risk after conservative surgery and radiotherapy for early-stage breast carcinoma.
Authors: Wazer D E , DiPetrillo T , Schmidt-Ullrich R , Weld L , Smith T J , Marchant D J , Robert N J 
Published: February 2017

PURPOSE The study was undertaken to assess the relationship among cosmesis and complications to factors related to disease presentation, surgical and radiotherapeutic technique, and adjuvant systemic therapy in conservative treatment for early-stage breast carcinoma. PATIENTS AND METHODS Between 1982 and 1988, 234 women with stage I/II breast carcinoma were treated with conservation therapy by a highly standardized protocol of limited excision and radiotherapy. Radiation boost and/or reexcision were determined by careful quantitation of the normal tissue margin around the primary tumor. Boosts to 20 Gy were preferentially performed with interstitial iridium-192 (192Ir) implants. Axillary node dissections were performed in all patients aged less than 70 years. Adjuvant therapy consisted of cyclophosphamide, methotrexate, (doxorubicin), and fluorouracil (CM[A]F) six to eight times for node-positive premenopausal women and tamoxifen for node-positive or -negative postmenopausal women. Median follow-up was 50 months (range, 20 to 80 months). Cosmesis was graded by defined criteria, and complications were individually scored. RESULTS Factors found to impact cosmesis adversely were palpable tumors (P = .046), volume of breast tissue resected (P = .027), reexcision of the tumor bed (P = .01), number of radiation fields (P = .03), radiation boost (P = .01), and chest wall separation (P = .01). There was a trend toward worse cosmesis (P = .062) in patients receiving tamoxifen. Cosmesis was not adversely affected by interstitial implant in spite of a higher prescribed dose. Factors influencing complication risk were axillary node dissection (P = .02), number of lymph nodes harvested (P = .05), and chemotherapy (P = .03). CONCLUSIONS Optimal cosmesis and minimal complication risk require careful attention to the technical details of surgery and radiotherapy. The impact of systemic therapies needs to be more thoroughly examined.
2-Chlorodeoxyadenosine treatment of low-grade lymphomas.
Authors: Kay A C , Saven A , Carrera C J , Carson D A , Thurston D , Beutler E , Piro L D 
Published: February 2017

PURPOSE Because of the need to identify effective new agents in the treatment of non-Hodgkin's lymphoma and because of the high activity of the purine analog 2-chlorodeoxyadenosine (2-CdA) against chronic lymphocytic leukemia and hairy cell leukemia, a phase II trial of 2-CdA was initiated in patients with low-grade lymphocytic lymphomas. PATIENTS AND METHODS Forty patients with low-grade lymphocytic lymphomas including diffuse small lymphocytic, follicular small-cleaved, and follicular mixed histologies were enrolled onto the study. Conventional therapies had failed in all patients, and six patients had lymph node biopsies showing evidence of histologic evolution to a higher-grade lymphoma. A total of 107 courses of 2-CdA were administered. There were 27 males and 13 females. The median age was 59 years (range, 37 to 80 years). Patients had received a median of three prior therapies (range, one to six therapies). RESULTS An overall response rate of 43% was achieved, with eight patients experiencing complete responses (CRs) and nine patients experiencing partial responses (PRs). The duration of responses ranged from 1 to greater than 33 months without maintenance therapy (median duration of response, 5 months). Histology and prior therapy history did not seem to correlate with responses. Significant toxicity was limited to bone marrow suppression; 18% of patients developed neutropenia, and 30% developed thrombocytopenia. CONCLUSIONS This phase II trial demonstrates that 2-CdA is an effective antilymphocyte, antineoplastic agent with significant activity as a single agent in patients with recurrent or refractory low-grade lymphocytic lymphoma. Responses were achieved with an acceptable toxicity profile. Further trials of this agent in previously untreated patients and in combination regimens are indicated and will be developed.
Preradiation intracarotid cisplatin treatment of newly diagnosed anaplastic gliomas. The CNS Cancer Consortium.
Authors: Dropcho E J , Rosenfeld S S , Morawetz R B , Vitek J , Brothers M , Gorum T , Bell S , Gillespie G Y , Glantz M , Mahaley M S 
Published: February 2017

PURPOSE This phase II study was performed to assess the response of patients with newly diagnosed, untreated malignant gliomas (anaplastic astrocytoma [AA] and glioblastoma multiforme [GBM]) to intracarotid (IC) cisplatin. PATIENTS AND METHODS Eligibility criteria included surgical intervention limited to biopsy only, measurable contrast-enhancing tumor, and unilateral tumor location within the vascular territory of one internal carotid artery. Patients were scheduled to receive four infusions of IC cisplatin (75 mg/m2 every 4 weeks) before beginning standard radiotherapy. Twenty-six patients were treated, and 22 were assessable for response. RESULTS Ten patients (45%) showed a greater than 25% decrease in the enhancing tumor area before radiotherapy with stabilization or improvement of neurologic deficits, and three patients (14%) had a greater than 70% decrease in tumor area. The likelihood of response to IC cisplatin was not clearly linked to patient age, tumor histology, or pretreatment tumor size. Myelosuppression, nephrotoxicity, and ototoxicity were mild. Optic neuropathy occurred in one patient, seizures in two, and fatal postinfusion cerebral edema in one. CONCLUSION This study design, which permits assessment of the drug sensitivity of the untreated glioma, has shown definite antitumor activity of IC cisplatin in newly diagnosed malignant glioma patients.
Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: the case for studies in previously treated patients.
Authors: Grant S C , Gralla R J , Kris M G , Orazem J , Kitsis E A 
Published: February 2017

PURPOSE This review was undertaken (1) to determine the antitumor activity of agents studied in phase II trials in small-cell lung cancer (SCLC) patients, (2) to evaluate the adequacy of published trials, (3) to determine if previously treated patients are suitable for phase II trials in SCLC, and (4) to develop an improved design for phase II trials. DESIGN English-language, single-agent efficacy trials in SCLC, published from 1970 to 1990, were reviewed. Study design and reporting of results were assessed for clinical and statistical methodology. Response rates observed in previously treated patients were compared with those observed in previously untreated patients. RESULTS One hundred forty-one articles evaluating 57 agents in 3,042 patients were reviewed. Eleven drugs were active (defined as a response rate greater than or equal to 20% in a trial with greater than or equal to 14 assessable patients), and 12 were inactive. Due to methodologic problems with the clinical trials, the usefulness of the remaining 34 drugs (60%) remains uncertain. Deficiencies identified in trials include inappropriate sample sizes, poorly defined response criteria, and failure to report important prognostic factors. When studied in adequate trials, all agents known to be active in SCLC had an observed response rate greater than or equal to 10% in previously treated patients. CONCLUSIONS Over the past 2 decades, phase II trials in SCLC have failed in their primary task of effectively identifying agents that warrant further clinical study and rejecting inactive agents. If only previously treated patients had been entered into these trials, no useful agent would have been missed provided that a lower observed response rate had been used as evidence of antitumor activity. We propose a two-stage sequential study design, entering previously treated patients, for future phase II trials in SCLC.
Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature.
Authors: Smith D C , Tucker J A , Trump D L 
Published: February 2017

PURPOSE Hypercalcemia is a rare complication of prostate cancer, and no definite association with any histologic subtype of prostatic malignancy has been documented. We have recently seen three patients who developed hypercalcemia in the setting of prostate cancer. All had neuroendocrine carcinoma of the prostate (NCPs), which prompted an exploration of the potential association of hypercalcemia with NCP. DESIGN An extensive review of literature published in the English-language was conducted to identify cases of hypercalcemia associated with prostate cancer and well-documented cases of NCP. RESULTS We found 17 reported cases of hypercalcemia clearly associated with prostate cancer and a total of 61 cases of well-documented NCP. Including our cases, 11 of the 20 reported cases of hypercalcemia associated with prostate carcinoma were in patients with neuroendocrine carcinomas. CONCLUSION Hypercalcemia in the setting of prostate cancer should prompt a search for unusual histologies.
Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study.
Authors: Trueworthy R , Shuster J , Look T , Crist W , Borowitz M , Carroll A , Frankel L , Harris M , Wagner H , Haggard M 
Published: February 2017

PURPOSE Using the technique of recursive partitioning and amalgamation analysis with verification, the Pediatric Oncology Group (POG) investigated the independent prognostic significance of previously published prognostic factors significantly associated with event-free survival (EFS) in B-progenitor cell acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Age, leukocyte count, sex, immunophenotype (expression of cytoplasmic immunoglobulin [Ig] and of surface antigens CD10 and CD34), and DNA index (ratio of the flow cytometry-determined DNA content of leukemia cells to that of normal diploid cells) were the variables used in the evaluation of four antimetabolite-based chemotherapy regimens in 1,535 children with the newly diagnosed B-progenitor cell ALL between February 1986 and May 1990. RESULTS There were three subgroups at widely different risks of treatment failure. A DNA index greater than 1.16 was the most prognostic feature. The final prognostic subgrouping was as follows: (1) DNA index greater than 1.16; (2) DNA index less than or equal to 1.16, age less than 11.0 years, and leukocyte count less than 50 x 10(9)/L; and (3) DNA index less than or equal to 1.16, (age greater than 11.0 years, and/or leukocyte count greater than 50 x 10(9)/L). These groups made up 20%, 53%, and 27% of the patients and had 4-year EFS rates (SE) of 90.1% (6.3%), 80.5% (5.1%), and 50.4% (7.6%), respectively. CONCLUSIONS Use of the DNA index, leukocyte count, and age--data that are relatively inexpensive and simple to obtain--may be sufficient to stratify patients with B-progenitor cell ALL for risk-directed therapy. Patients at an extremely low risk of failing therapy (approximately 20% of cases in this study) can thus be identified and spared the toxic short-term and late effects of more intensive therapies that may be needed for children with less favorable clinical and biologic features.
Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma.
Authors: Redman J R , Cabanillas F , Velasquez W S , McLaughlin P , Hagemeister F B , Swan F , Rodriguez M A , Plunkett W K , Keating M J 
Published: February 2017

PURPOSE In a phase II trial we investigated fludarabine phosphate (FAMP) as therapy for patients with relapsed lymphoma to determine its effectiveness and toxicity in this disease. PATIENTS AND METHODS The 67 assessable patients had a median age of 56 years and had received a median of three chemotherapy regimens before treatment with FAMP. The starting dose was 25 mg/m2 administered intravenously over 30 minutes daily for 5 days every 3 to 4 weeks. RESULTS High response rates were observed for follicular small cleaved-cell lymphoma (FSCCL) (62%), follicular mixed small- and large-cell lymphoma (80%), and follicular large-cell lymphoma (FLCL) (100%). Responses also occurred in small lymphocytic lymphoma (SLL) (33%), transformed lymphoma (33%), mycosis fungoides (40%), and Hodgkin's disease (25%). No responses were observed in other intermediate- or high-grade lymphomas (N = 20). Overall, there were five patients with a complete response, 23 patients with a partial response, and an overall response rate of 37%. Toxicity was primarily hematologic and infectious. No significant gastrointestinal, hepatic, renal, or neurologic toxicity occurred. CONCLUSIONS We conclude that FAMP has major activity in follicular lymphoma. Fundamental research is needed to understand this differential efficacy in low-grade lymphoma yet lack of efficacy in intermediate- and high-grade lymphoma. Clinical investigations should be done using FAMP in varying dose schedules and in combination regimens.
Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies.
Authors: Rusch V W , Niedzwiecki D , Tao Y , Menendez-Botet C , Dnistrian A , Kelsen D , Saltz L , Markman M 
Published: February 2017

PURPOSE Intrapleural cisplatin-based chemotherapy has been used in the treatment of patients with malignant pleural mesothelioma and malignant pleural effusions, but the pharmacokinetics of this form of chemotherapy have not been previously evaluated. We performed pharmacokinetic studies on 12 patients who received both intrapleural cisplatin and mitomycin immediately following pleurectomy/decortication for malignant pleural mesothelioma. PATIENTS AND METHODS Simultaneous pleural fluid and plasma samples were collected at 15 and 30 minutes, and at 1, 2, 3, 4, and 24 hours after administration of the intrapleural chemotherapy (cisplatin 100 mg/m2 and mitomycin 8 mg/m2), and after cisplatin (total and free) and mitomycin levels were measured. The mean peak levels, the areas under the concentration-time curve (AUC) and the drug half-lives (t1/2s) in plasma and pleural fluid were compared using the paired t test. Differences were considered significant if P less than or equal to .05. RESULTS Systemic absorption was rapid, with peak plasma levels being reached within 1 hour of administration of the intrapleural chemotherapy. Peak plasma levels measured after intrapleural chemotherapy approximated those reportedly attained during systemic administration of these drugs at similar doses. However, the mean peak cisplatin and mitomycin levels, and their mean AUCs, were significantly higher in the pleural fluid than in the plasma. There was a three- to fivefold advantage (on a logarithmic scale) for pleural to plasma AUCs for both cisplatin and mitomycin. The mean t1/2s for cisplatin and mitomycin were significantly longer in the plasma than in the pleural fluid. CONCLUSIONS The pharmacokinetics of intrapleural cisplatin-based chemotherapy are analogous to those of intraperitoneal chemotherapy. Our findings show that intrapleural cisplatin-based chemotherapy has a distinct local pharmacologic advantage, but also produces significant and sustained drug plasma levels.