bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy followed by accelerated fractionated radiation for larynx preservation in patients with advanced laryngeal cancer.
Authors: Eisbruch A , Thornton A F , Urba S , Esclamado R M , Carroll W R , Bradford C R , Hazuka M B , Littles F J , Strawderman M , Wolf G T 
Published: February 2017

PURPOSE Larynx preservation in advanced, resectable laryngeal cancer may be achieved using induction chemotherapy (CT) followed in responding patients by definitive radiation (RT). To address potential accelerated repopulation of clonogenic tumor cells during the prolonged total treatment time, we studied the feasibility of accelerated fractionated RT after CT. METHODS Patients with advanced laryngeal cancer received two cycles of cisplatin 100 mg/m2 and fluorouracil (5-Fu) 1,000 mg/m2/d for 5 days. Responding patients received a third cycle after which those who had complete response or tumor down-staging to T1 proceeded with accelerated RT: 70.4 Gy delivered over 5.5 weeks. Patients who achieved a lesser response to CT underwent total laryngectomy and postoperative RT. RESULTS Thirty-three patients were accrued. Three died during the course of CT and two declined definitive treatment after CT. Twenty-one patients had a major response to CT, 20 of whom received accelerated RT. Median weight loss during RT was 11%. Late severe morbidity was observed in five patients (25%). All four patients who underwent salvage laryngectomy after accelerated RT experienced major postoperative complications. The locoregional failure rate was 25%. The larynx was preserved in 48% of the total study population and in 80% of the patients irradiated according to the study protocol. CONCLUSION Accelerated RT after CT as delivered in this study may increase both acute and long-term morbidity rates compared with studies using standard RT after CT. It did not seem to improve local/regional tumor control or survival despite stringent patient selection criteria.
Cisplatin-fluorouracil exclusive chemotherapy for T1-T3N0 glottic squamous cell carcinoma complete clinical responders: five-year results.
Authors: Laccourreye O , Brasnu D , Bassot V , Ménard M , Khayat D , Laccourreye H 
Published: February 2017

PURPOSE To evaluate cisplatin-fluorouracil exclusive chemotherapy (EC) for T1-T3N0 glottic squamous cell carcinoma complete clinical responders (CCR) after cisplatin-fluorouracil induction chemotherapy (IC). PATIENTS AND METHODS A retrospective analysis was performed of 58 patients with T1-T3N0 glottic squamous cell carcinoma CCR after IC consecutively managed at our department between 1985 and 1992. Twenty-one CCR were managed with EC. Thirty-seven CCR were managed with IC and a conventional laryngeal-preservation modality. Analyses of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor were performed using the Kaplan-Meier actuarial life-table method. In CCR managed with EC, the independent factors of age, tumor classification, exact tumor location, true vocal cord motion, arytenoid cartilage motion, total dosage of drugs delivered, and number of courses received were tested for potential correlation with survival, local recurrence, nodal recurence, and distant metastasis. RESULTS The 5-year survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor rates in CCR managed with EC were 95.2%, 70.7%, 0%, 0%, and 14.3%, respectively. The 5-year rates of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor in CCR managed with IC and a conventional laryngeal-preservation modality were 86.1%, 97%, 2.7%, 6%, and 14.5%, respectively. Local recurrence was statistically more likely in CCR managed with EC (P = .002). Local recurrence in CCR managed with EC was always salvaged with partial laryngectomy or radiation therapy, which resulted in an overall 100% local control and laryngeal-preservation rate within this group. In CCR managed with EC, none of the variables analyzed was statistically related to survival, local recurrence, nodal recurrence, or distant metastasis. CONCLUSION The present retrospective studies demonstrated that within T1-T3N0 glottic squamous cell carcinoma CCR, there is clearly a significant subset of patients with chemocurable tumors who achieved both perfect preservation of structure-supporting voice and long-term survival after EC. Careful monthly follow-up evaluation allowed for timely successful salvage of local recurrence after EC without the need for total laryngectomy. Such management did not appear to increase the risk for subsequent nodal failure, subsequent distant metastasis, or reduced survival.
Phase I trial and pharmacologic trial of sequences of paclitaxel and topotecan in previously treated ovarian epithelial malignancies: a Gynecologic Oncology Group study.
Authors: O'Reilly S , Fleming G F , Barker S D , Walczak J R , Bookman M A , McGuire W P , Schilder R J , Alvarez R D , Armstrong D K , Horowitz I R , Ozols R F , Rowinsky E K 
Published: February 2017

PURPOSE A phase I and pharmacologic study to evaluate the feasibility of administering paclitaxel (PTX) in combination with topotecan (TPT) without and with granulocyte colony-stimulating factor (G-CSF) in women with recurrent or refractory ovarian cancer. PATIENTS AND METHODS TPT was administered as a 30-minute infusion daily for 5 days and PTX was given as a 24-hour infusion (PTX-24) either before TPT on day 1 or after TPT on day 5. Each patient received both schedules on an alternating basis every 3 weeks. Sequential dose escalation of TPT or PTX-24 without and with G-CSF resulted in five dosage permutations of TPT/PTX (mg/ m2): 0.75/135 without G-CSF and 0.75/135, 1.25/135, 1.50/135, and 1.25/170 with G-CSF. RESULTS Twenty-two patients received 109 courses of therapy. Dose-limiting myelosuppression consistently occurred at the first TPT/PTX-24 dose level (0.75/135 mg/m2) in the absence of G-CSF support. Although the addition of G-CSF resulted in reduced rates of complicated neutropenia, the incidences of dose-limiting neutropenia and thrombocytopenia were unacceptably high after the doses of either TPT or PTX-24 were increased. Paired analysis showed similar hematologic toxicities between the two sequences of drug administration. The pharmacologic behavior of both TPT and PTX-24 was not altered by drug sequencing. Major antitumor responses occurred in 40% of patients with measurable and assessable disease, including 45% and 9% of patients with potentially cisplatin-sensitive and -resistant tumors, respectively. CONCLUSION The recommended doses of TPT on a daily times-five schedule combined with PTX-24 in these patients were 0.75 mg/m2/d and 135 mg/m2, respectively, with G-CSF support. Although this dose of PTX has significant single-agent activity in ovarian cancer, the dose of TPT is much lower than the TPT dose at which single-agent activity has been observed. Due to the inability to administer near relevant single-agent doses of both drugs in combination, as well as the requirement for G-CSF support, further evaluations of this regimen in women with refractory or recurrent ovarian cancer are necessary before it can be recommended for previously treated patients in this setting.
Dose-effect study of carboplatin in ovarian cancer: a Danish Ovarian Cancer Group study.
Authors: Jakobsen A , Bertelsen K , Andersen J E , Havsteen H , Jakobsen P , Moeller K A , Nielsen K , Sandberg E , Stroeyer I 
Published: February 2017

PURPOSE To elucidate the effect of a doubled carboplatin dose-intensity in epithelial ovarian cancer in combination with a fixed dose of cyclophosphamide. PATIENTS AND METHODS A total of 222 patients with epithelial ovarian cancer stages II to IV were included in the study. Following surgery, patients were randomly assigned to receive carboplatin at an area under the concentration-versus-time curve (AUC) of 4 (AUC4) or carboplatin at an AUC of 8 (AUC8) and cyclophosphamide 500 mg/m2 given every 4 weeks for six courses. The AUC was calculated according to Calvert's formula. In 123 patients, the carboplatin AUC was also measured based on a single-sample method and the results were compared with the calculated AUC. The end points of the trial were complete pathologic remission (CPR) and crude survival. RESULTS Approximately 50% of patients in both arms underwent second-look surgery. The frequency of CPR was 32% and 30%, respectively. The survival curves showed no significant difference (P = .84). The dose-intensity of cyclophosphamide was almost identical in the two arms, whereas that of carboplatin was different. In the AUC8 arm, the dose-intensity was 1.86 times that of the AUC4 arm. The results also demonstrated good agreement between the calculated and the measured AUC in most patients. Bone marrow toxicity was significantly higher in the AUC8 arm. CONCLUSION A doubling of the carboplatin dose-intensity did not result in any significant improvement of pathologic remission or survival. Calvert's formula can be used to give a fairly accurate estimate of the carboplatin AUC. Bone marrow toxicity increased with higher dose-intensity, and a further increase of dose is only feasible with growth-factor or stem-cell support.
Complications after treatment with external-beam irradiation in early-stage prostate cancer patients: a prospective multiinstitutional outcomes study.
Authors: Beard C J , Propert K J , Rieker P P , Clark J A , Kaplan I , Kantoff P W , Talcott J A 
Published: February 2017

PURPOSE To use data from a prospective quality-of-life study to assess differences in disease-specific and general health-related quality-of-life changes after treatment with different external-beam irradiation techniques for prostate cancer. PATIENTS AND METHODS Patients were divided into three groups based on their pretreatment field size and planning technique: whole pelvis, small field, or conformal. Measures of bowel, urinary, and sexual function and of global health-related quality-of-life parameters (from the Health Survey Short Form [SF-36] and the Profile of Mood States [POMS]) were obtained from self-report questionnaires completed before initiation of therapy and at 3 and 12 months after therapy. RESULTS Irritative gastrointestinal and genitourinary side effects were frequent 3 months after treatment, but were substantially improved at 12 months. Sexual dysfunction increased steadily over the study period. The POMS and the SF-36 did not demonstrate significant changes over time. Despite small patient numbers, we found trends in favor of conformal therapy across several symptom measures, including sexual function. In the fatigue, energy, and vigor subscales, patients who received whole-pelvis treatment fared significantly worse than those in the other two groups. CONCLUSION Prospective, detailed data from a feasibility study allowed us to assess the effect of technique on quality of life following external-beam irradiation. Although limited by the small planned sample size, these results suggest that smaller radiation fields limit treatment-related complications, including, unexpectedly, sexual dysfunction. However, confirmation in a larger study is necessary.
Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy.
Authors: Rougier P , Bugat R , Douillard J Y , Culine S , Suc E , Brunet P , Becouarn Y , Ychou M , Marty M , Extra J M , Bonneterre J , Adenis A , Seitz J F , Ganem G , Namer M , Conroy T , Negrier S , Merrouche Y , Burki F , Mousseau M , Herait P , Mahjoubi M 
Published: February 2017

PURPOSE To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients. PATIENTS AND METHODS Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function. RESULTS Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern. CONCLUSION CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.
Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.
Authors: Webb A , Cunningham D , Scarffe J H , Harper P , Norman A , Joffe J K , Hughes M , Mansi J , Findlay M , Hill A , Oates J , Nicolson M , Hickish T , O'Brien M , Iveson T , Watson M , Underhill C , Wardley A , Meehan M 
Published: February 2017

PURPOSE We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were randomized and analyzed for survival, tumor response, toxicity, and quality of life (QL). RESULTS The overall response rate was 45% (95% confidence interval [CI], 36% to 54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was tolerable and there were only three toxic deaths. The FAMTX regimen caused more hematologic toxicity and serious infections, but ECF caused more emesis and alopecia. The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95% CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The global QL scores were better for ECF at 24 weeks, but the remaining QL data showed no differences between either arm of the study. Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $975 per life-year gained. CONCLUSION The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.
Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study.
Authors: al-Sarraf M , Martz K , Herskovic A , Leichman L , Brindle J S , Vaitkevicius V K , Cooper J , Byhardt R , Davis L , Emami B 
Published: February 2017

PURPOSE The present intergroup phase III randomized study compared combined chemotherapy (CT) plus radiotherapy (RT) treatment versus RT only in patients with locally advanced esophageal cancer. MATERIALS AND METHODS Two courses of chemotherapy during 50 Gy RT followed by additional two courses of the same CT, versus 64 Gy RT alone were investigated. CT consisted of cisplatin 75 mg/m2 on day 1 [corrected] and fluorouracil (5FU) 1,000 mg/m2/d on days 1 to 4 every 4 weeks with RT and every 3 weeks post-RT. The main objective of the study was to compare overall survival between the two randomized treatment groups. Patients were stratified by tumor size, histology, and degree of weight loss. RESULTS Sixty-two assessable patients were randomized to receive RT alone, and 61 to the combined arm. Patients characteristics were as follows: squamous cell cancer, 90% versus 85%; weight loss greater than 10 lb, 61% versus 69%; and tumor size, > or = 5 cm, 82% versus 80% on the RT and CT-RT arms, respectively. Systemic side effects, which consisted of nausea, vomiting, and renal and myelosuppression, occurred more frequently on the combined arm, while local side effects were similar in both groups. With a minimum follow-up time of 5 years for all patients, the median survival duration was 14.1 months and the 5-year survival rate was 27% in the combined treatment group, while the median survival duration was 9.3 months with no patients alive at 5 years in the RT-alone group (P < .0001). Additional patients (69) were treated with the same combined therapy and were analyzed. The results of the last group confirmed all of the results obtained with combined CT-RT in the randomized trial, with a median survival duration of 17.2 months and 3-year survival rate of 30%. CONCLUSION We conclude that cisplatin and 5FU infusion given during and post-RT of 50 Gy is statistically superior to standard 64-Gy RT alone in patients with locally advanced esophageal cancer.
Dose-intensive weekly chemotherapy for treatment of relapsed small-cell lung cancer.
Authors: Kubota K , Nishiwaki Y , Kakinuma R , Hojo F , Matsumoto T , Ohmatsu H , Sekine I , Yokozaki M , Goto K , Ebi N , Kodama T 
Published: February 2017

PURPOSE This study was undertaken to determine the activity and toxicity of dose-intensive weekly chemotherapy (cisplatin, vincristine, doxorubicin, and etoposide [CODE] regimen) for previous treated, recurrent small-cell lung cancer (SCLC). PATIENTS AND METHODS The 17 patients with relapsed SCLC entered onto the study were to receive intensive weekly chemotherapy with the CODE regimen. All 17 patients had been heavily pretreated with some form of cisplatin-based combination chemotherapy. Six patients had received previous chemotherapy with CODE and one patient with cisplatin and etoposide (PE) as induction therapy. Nine patients had been treated with concurrent or sequential PE plus thoracic irradiation (TRT). The median time off chemotherapy was 6.7 months (range, 3.3 to 72). Patients were treated with 9 weeks of the CODE regimen. Response, survival, and toxicity data were noted. RESULTS All 17 patients were assessable for response, survival, and toxicity. Fifteen of 17 patients (88.2%) had an objective response, with five complete responses (CRs; 29%) and 10 partial responses (PRs; 58.8%). The median durations of response and survival were 156 days and 245 days, respectively. Myelosuppression was significant, with 76% of patients developing grade 4 leukopenia. No treatment-related death was observed. CONCLUSION The CODE regimen is highly active in the treatment of relapsed SCLC with an encouraging survival outcome.
Maximum-tolerated dose defined for single-agent gemcitabine: a phase I dose-escalation study in chemotherapy-naive patients with advanced non-small-cell lung cancer.
Authors: Fossella F V , Lippman S M , Shin D M , Tarassoff P , Calayag-Jung M , Perez-Soler R , Lee J S , Murphy W K , Glisson B , Rivera E , Hong W K 
Published: February 2017

PURPOSE We conducted a phase I trial of the novel nucleoside analog, gemcitabine, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose and efficacy in this population. PATIENT AND METHODS Eligibility requirements included stage III or IV NSCLC, performance status < or = 1, and no prior chemotherapy. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks every 4 weeks. We enrolled patients at doses that ranged from 1,000 to 2,800 mg/m2/wk (three patients per cohort). Responses were assessed after every two courses (8 weeks). RESULTS We treated 33 chemotherapy-naive patients with stage III (n = 5) or IV (n = 28) NSCLC. Most had performance status 1, and 67% had adenocarcinoma. Eight of 32 assessable patients (25%) achieved a partial response. The projected median survival duration (all patients) is 49 weeks. The maximum-tolerated dose was 2,200 mg/m2/wk for 3 weeks every 4 weeks; dose-limiting toxicity was myelosuppression and reversible transaminase elevation. Other side effects were consistently mild. The maximum dose-intensity achieved with the first two cycles was 2,362 mg/m2/wk for 3 weeks every 4 weeks, which is a feasible phase II starting dose. CONCLUSION This study estimates a phase II starting dose of gemcitabine in chemotherapy-naive patients to be 2,400 mg/m2/wk for 3 consecutive weeks every 4 weeks; this is much higher than that previously reported in heavily pretreated patients. Twenty-five percent of patients with advanced NSCLC achieved a partial response to gemcitabine. This significant activity in conjunction with a very favorable toxicity profile supports the further evaluation of gemcitabine in combination with other active agents.