Cycles Of CT Research Articles

Chemotherapy intensification in patients with advanced seminoma and adverse prognostic factors.

The aim of our study was to identify factors which influence survival in patients with disseminated seminoma in the good prognostic group according to IGCCCG, as well as to evaluate the impact of treatment intensification in patients with negative prognostic factors. We analyzed the database of the patients with metastatic seminoma who had received treatment at our department from 1986 to 2005. Inclusion criteria were as follows: morphologically verified seminoma; favorable prognosis according to IGCCCG; modern chemotherapy regimen (EP ± bleomycin); AFP level <15 IU/ml; and HCG level <300 mIU/ml. The primary endpoint was overall survival (OS). With median follow-up 83 months, 5-year OS rate was 91% in 206 patients. Only three negative prognostic factors were associated with OS: retroperitoneal lymph nodes >5 cm (p < 0.01), pulmonary metastases (p < 0.01) and LDH level ≥ 2.25 × ULN (p = 0.01). In view of the obtained data, we have changed our treatment approach since 2005. In case of any negative prognostic factors, we administered an intensified CT regimen--4BEP or 3BEP + 1EP. Prospective phase of the study included 34 patients with unfavorable prognosis. We observed an increase of 5-year OS rate in the intensified CT group in comparison with the standard CT group in patients with unfavorable prognostic from 85 to 100%. Administration of 4 cycles of induction CT (4BEP or 3BEP + 1EP) in patients with metastatic seminoma who have LDH level ≥ 2.25 ULN, and/or retroperitoneal lymph nodes >5 cm and/or pulmonary metastases results in decreased disease progression rate and significant gain in OS.

Quality of life (QoL) in patients with malignant dysphagia: An international randomized trial comparing radiotherapy alone (RT) versus chemoradiotherapy (CRT)—TROG03.01 NCICCTG ES2.

163 Background: The dominant symptom for pts with esophageal cancer is dysphagia. Palliative radiotherapy is commonly employed for symptom relief. We report the effect on QoL in our study comparing a 2-3 week course of RT alone vs the same RT with a single cycle of concomitant CT. Methods: 220 pts with malignant dysphagia were randomized to receive RT (30-35Gy in 10-15 fr) (n=109) ± concomitant CT (5FU and cisplatin D1-4) cycle. The primary outcome was dysphagia relief. QoL was evaluated using EORTC QLQ30/OES18 at baseline, wk 9, 13 and mthly x1yr. Group mean scores were compared between arms using Wilcoxon Rank-Sum test. Proportion of pts with improved, stable or worsened QoL (≥10 point change at any time compared with baseline) using chi square and MH chi-square test (for trend), while time to dysphagia improvement was compared using K-M estimates. Results: QoL compliance ranged from 77% (169/220) at baseline to 62% (36/58) at mth12 and was similar between groups. Baseline mean scores were equivalent between arms with the exception of physical [79 (SD19) CRT vs. 83.84 (SD19) RT; p=0.016] and role domains [61 (SD34) CRT vs. 72 (SD32) RT; p = 0.01]. There was no significant difference in QoL between the arms. The proportion of pts with improvement in the dysphagia domain was 50% CRT vs 64% RT (ns) while the time to improvement was 2.6m CRT vs 2.3m RT (ns). The eating domain was improved in 68% CRT and 74% RT (ns) while global QoL was 46% in both arms. Other symptom domains/items that were improved in more than half of the pts included 62% in pain and 52% in appetite. Functional domain improvements were moderate ranging from 41% emotional, 39% role, 38% social, 28% cognitive to 18% physical (average of scores in both arms). Conclusions: QoL data showed improvement in domains associated with nutritional intake for 50-70% of pts depending on the symptom measured. This was accompanied by moderate improvement in functional domains. No significant benefit was observed when CT was added to RT alone. Clinical trial information: NCT00193882.

856P - Chemotherapy (Ct) Intensification in Patients (Pts) with Metastatic Seminoma Who Have Negative Prognostic Factors

ABSTRACT Aim: Administration of 3 cycles of BEP or 4 cycles of EP CT is recommended for pts with metastatic seminoma and good prognosis by IGCCCG. The aim of our study was to identify prognostic factors which influence survival in pts with disseminated seminoma in the good prognostic group according to IGCCCG, as well as to evaluate the impact of treatment intensification in pts with negative prognostic factors. Methods: We analyzed the database of the pts with metastatic testicular seminoma who had received treatment at our department from 1986 to 2005. Inclusion criteria were: morphologically verified seminoma; favorable prognosis according to IGCCCG; modern chemotherapy regimen (EP +/- bleomycin); AFP level before CT lower than 15 IU/ml; HCG level before CT lower than 300 mIU/ml. The primary endpoint was overall survival (OS). All statistical analysis was performed using Statistical Package for the Social Sciences software program (version 17.0; SPSS Inc.Chicago, IL). Results: Two hundred and six pts met the inclusion criteria. With median follow-up 83 months (range: 2-244) disease progression had 12.1% of pts and 5-year OS rate was 91%. Only three negative prognostic factors were associated with OS: pre-CT retroperitoneal lymph nodes larger than 5 cm (HR 5.3, р Conclusions: Administration of 4 cycles of induction CT (4ВЕР or 3ВЕР + 1ЕР) in pts with metastatic seminoma who have high LDH level (≥2,25 UNL), and/or retroperitoneal lymph nodes >5 cm and/or pulmonary metastases results in decreased disease progression rate and significant gain in OS. Disclosure: All authors have declared no conflicts of interest.

Updated Analysis of Response and Patient-Reported Outcomes (Pro) in Two Large Open-Label, Phase III Studies (Lux-Lung 3 [Ll3] and Lux-Lung 6 [Ll6]) of Afatinib (A) Versus Chemotherapy (Ct) in Patients (Pts) with Advanced Nsclc Harboring Egfr Mutations (Mut)

ABSTRACT Aim: A, an oral, irreversible ErbB family blocker of EGFR, HER2, ErbB3 and ErbB4 signalling, improved progression-free survival (PFS), showed higher objective response rates (ORR), faster time to response (TTR) and favourable trends in PROs versus cisplatin/pemetrexed (LL3; 345 pts recruited globally) and cisplatin/gemcitabine (LL6; 364 Asian pts) in treatment-naive pts with stage IIIB/IV EGFR mut positive NSCLC. We present an updated analysis of PFS, response and PRO data. Methods: Pts were randomized 2:1 to 40 mg A or up to 6 cycles of CT. The primary endpoint was PFS; secondary endpoints included ORR and PROs. PROs were assessed by EORTC QLQ-C30 and QLQ-LC13 questionnaires from randomization until disease progression. Updated PFS, response and PRO analyses were completed at the time of primary OS analysis, during which 21 (LL3) and 23 (LL6) pts were still on A treatment. Results: Updated PFS analysis confirmed superiority of A in both trials. ORR, TTR and PRO analyses were consistent with earlier findings. ORR was 57% [A] vs 23% [CT] in LL3; 68% [A] vs 23% [CT] in LL6. Of those with OR, pts treated with A responded faster than those treated with CT, with response reported at the time of first imaging (week 6) in 72% vs 58% in LL3 and 73% vs 57% in LL6. Worsening of cough and dyspnea was significantly delayed with A vs CT. A greater magnitude of effect on PROs with A was seen in pts with common EGFR mut. Median time to deterioration (months) in symptoms of cough, dyspnea and pain LL3 LL6 A C/P HR; p-value A G/C HR; p-value All randomised Cough 27.0 8.0 0.59; 0.006 31.1 10.3 0.46; Dyspnea 10.4 2.9 0.68; 0.013 7.7 1.7 0.53; Pain 4.2 3.1 0.83; 0.188 6.9 3.4 0.70; 0.022 Common mutations Cough Not estimable 10.2 0.51; 0.001 31.1 Not estimable 0.43; Dyspnea 14.5 2.7 0.54; 8.3 1.7 0.53; Pain 4.8 3.1 0.74; 0.052 6.4 2.7 0.67; 0.016 Conclusions: In addition to significant delay in disease progression, A induces a superior and faster response in pts with EGFR mut NSCLC and leads to long-lasting control and delay in worsening of lung cancer symptoms vs CT. Disclosure: L.V. Sequist: Uncompensated Advisory boards for: Boehringer Ingelheim, AstraZeneca, Merrimack, Novartis, Taiho; J. Feng: Corporate sponsored research for Boehringer Ingelheim; S. Lu: Advisory boards for: AstraZeneca and Boehringer Ingelheim; M. Schuler: Advisory boards for AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer Corporate sponsored research for Boehringer Ingelheim, Novartis Other substantive relationships with University Duisburg-Essen (Patents); T. Mok: Advisory boards for AZ, Roche, Eli Lilly, Merck Serono, Eisai, BMS, AVEO, Pfizer, Taiho, BI, Novartis, GSK Biologicals, Clovis Oncology, Amgen, Janssen, BioMarin Pharmaceutical Board of directors on IASLC Corporate sponsored research for AZ; N. Yamamoto: Other substantive relationships with TAIHO, ONO, CHUGAI, Pfizer, Eli Lilly, AstraZeneca, Boehringer Ingelheim; K.J. O'Byrne: Advisory Board, Travel expenses and Honoraria for: Boehringer Ingelheim; V. Hirsh: Advisory board for: Boehringer Ingelheim; C. Zhou: Advisory boards for Boehringer Ingelheim, F. Hoffmann-La Roche, Eli Lilly; D. Massey: Employee of Boehringer Ingelheim Ltd; J. Lungershausen: Employee of Boehringer Ingelheim GmbH; J. Yang: Advisory boards for Astrazeneca, Boehringer Ingelheim, Roche/Genentech, Merck Serono, Pfizer, Clovis Oncology, Novartis, Eli Lilly, Takeda, Innopharma, Bayer Corporate sponsored research for Boehringer Ingelheim. All other authors have declared no conflicts of interest.

An Exploratory Phase 2 Study of Pemetrexed (Pem) and Cisplatin (Cis) As Preoperative Chemotherapy (Ct) in the Treatment of Stage Iiian2 Nonsquamous Non-Small Cell Lung Cancer (Ns Nsclc)

ABSTRACT Aim: This study was designed to evaluate the response rate of Pem-Cis as preoperative CT in patients with stage IIIAN2 NS NSCLC. The neoadjuvant setting provided the opportunity to obtain tumor tissue samples for exploratory analyses of specific biomarkers pre and post CT. Methods: This single arm, multicenter Phase II study evaluated 3 cycles of preoperative Pem-Cis CT followed by surgery in patients with stage IIIAN2 NS NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. Patients received Pem 500 mg/m2 + Cis 75 mg/m2 IV on Day 1 Q3W with vitamin and dexamethasone supplementation and then underwent surgery. The primary endpoint was the overall response rate (ORR: complete response [CR] + partial response [PR]) after 3 CT cycles. A total of 33 patients were planned for enrolment. Secondary endpoints included pathological complete resection rate after surgery, tumor downstaging, and association between ORR and biomarker mRNA and protein expression (TS, TTF 1, E2F1, ERCC1, and BRCA1). Results: Patient enrolment was stopped early due to difficulties in identifying suitable patients. Of 19 enrolled patients (median age 62 years male/female 68%/32%, ECOG PS 0/1 79%/21%, adenocarcinoma 90%), 17 (89.5%) completed CT, and 15 (78.9%) completed CT and surgery. The ORR was 41.2% (95% CI: 18.4, 67.1%), all PRs. Of 17 patients with available scans 10 (58.8%) experienced tumor downstaging (stage IIIAN2 to IIIA, II, or I). Out of 15 patients undergoing surgery, 14 had a pathological complete resection resulting in a complete resection rate of 93.3% (95% CI: 68.1, 99.8%). No new safety signals were identified. Other efficacy outcomes are still immature. Conclusions: Pre-operative CT with Pem-Cis is active in patients with stage IIIAN2 NS NSCLC. The ORR of 41.2% is consistent with previous reports in this patient population. Assessment of the associations between ORR and baseline biomarker expression is ongoing. Disclosure: M. Das: MD is an employee and stock holder of Eli Lilly and Company; V. Soldatenkova: VS is an employee and stock holder of Eli Lilly and Company; C.M. Visseren-Grul: CVG is an employee and stock holder of Eli Lilly and Company; G. Scagliotti: GS has participated on advisory boards for Eli Lilly and Company, Astra Zeneca, Pfizer, and Roche. All other authors have declared no conflicts of interest.

Cisplatin + Vinorelbine Treatment of Recurrent or Metastatic Salivary Gland Malignancies (Rmsgm): a Final Report on 60 Cases

ABSTRACT Aim: RMSGM are not suitable for conventional treatment. We report the clinical outcomes of 60 patients affected by RMSGM who were treated with DDP + VNB as a first- or second-line scheme. Methods: Sixty patients between 2001 and 2008, affected by RMSGM were enrolled in this cohort prospective study; they received the following first- or second-line CT, for a maximum of 6 cycles: DDP at 80 mg/m2 on d 1 + VNB at 25 mg/ m2 on d 1 and 8, at 3-wk intervals. Results: Seventy percent of the patients received DDP + VNB as the first-line CT and 30% of them received it as the second-line CT. After 5 cycles (median) of first-line DDP + VNB, 7% of the patients achieved a CR, 24% achieved a PR, 33% achieved an NC and 36% achieved a PD. After 4 cycles (median) of second-line CT, 0 patients achieved a CR, 5% achieved a PR, 33% achieved an NC and 62% achieved a PD. The median OS period was 10 months for those who received the first-line CT and 4 months for those who received the second-line CT. The best ORR (54%) and median survival were observed, during first line treatment, in adenocarcinomas, whereas undifferentiated tumours were unresponsive with a poor median survival (4.6 months). Conclusions: Adenocarcinomas show the best response and prognosis with DDP + VNB scheme that seems to be an effective and well-tolerated first-line CT for RMSGM, whereas it has only low palliative activity as a second-line CT. Disclosure: All authors have declared no conflicts of interest.

Postoperative chemoradiation FOLFOX 4-based for R1 resected gastric cancer: A retrospective mono-institutional study.

143 Background: Improved DFS and OS were seen in curatively resected patients (pts.) with gastric and gastroesophageal adenocarcinoma treated with the Int0116 protocol of postoperative adjuvant chemoradiotherapy compared to surgery alone. However, there are very limited data about the efficacy of this approach in pts. with R1 resection. To evaluate the efficacy of a combined chemoradiation regimen in this setting, we reviewed our case records from 43 pts. with R1 resection treated between May 2008 and July 2012. Methods: 43 pts. with histologically confirmed gastric adenocarcinoma, received combined adjuvant chemotherapy with FOLFOX-4 for 8 cycles and concomitant radiotherapy (45 Gy in 25 daily fractions over 5 weeks). Radiotherapy was begun after 2 cycles of CT, (reduced by 20% during the period of concomitant radiotherapy). Pts. were followed at 3-month intervals for 2 years, at 6-month intervals for the next 3 years and yearly thereafter. Results: The median age was 62 years (range, 22-74) and the majority of pts. (76.7%) were males. Tumor location was equally distributed in the stomach. Most of the patients had locally advanced disease: 93% had T3-4 tumors and 74.4% had lymph node involvement. There was no treatment related death. Gastrointestinal G3 toxicity was observed in 11.6% of pts., while haematologic G3-4 toxicity was observed in 9.3%. Experienced toxicities led to chemotherapy dose reductions in 9 pts. and dose delay in 11 patients; 7 pts. had a delay in radiotherapy. With a median follow-up of 36 months (range 2-49) for the 43 R1 pts., 74.4% died of gastric cancer, 11.6% are alive with no evidence of recurrence and 13.9% are alive with disease. 66.6% of the relapses in this group occurred at distant sites and 33.3% were locoregional. The estimated 3-year OS was 19%. The median DFS was 14.5 months and the median OS was 16 months. Conclusions: These results seem to imply some benefit for the postoperative treatment, as nearly 19% of the R1 pts. in our study remained free of recurrence at 3 years from surgery. In the absence of phase III data and consequently lack of clear guidelines in this setting, our results support the common practice of adding postoperative chemoradiation after R1 gastrectomy.

Comparative study among glutamine, acetyl-L-carnitine, vitamin-E and methylcobalamine for treatment of paclitaxel-induced peripheral neuropathy

Context: One of the major toxicity of paclitaxel is peripheral neuropathy. Sensory components are affected more than motor and autonomic dysfunction. Aims: Acetyl-L-carnitine (ALC), methylcobalamine, vitamin E and glutamine have been used in various trials against placebos. With head on trials among these four drugs missing, this randomized study was conducted to compare the efficacy in relieving symptoms of paclitaxel induced peripheral neuropathy. Settings and Design : This single institutional, prospective, multi-arm, randomized study was conducted as per Helsinki protocol and with local ethical committee clearances. Materials and Methods: Patients of carcinomas of lung, breast and ovary recruited, would receive paclitaxel 175 mg/m 2 intravenous as 1 st or 2 nd line drug. They underwent randomization to any of four treatment arms: Arm A (vitamin E 400 mg OD day 1 of the cycle to 1 month after completion of clinical trial [CT]); Arm B (ALC 250 mg OD from day 1 to day 7 in each cycle of CT); Arm C (glutamine 10 mg TDS from day 2 to day 5 in each cycle) and Arm D (methylcobalamine 500 μg TDS from day 1 of the first cycle to 1 month after completion of CT). All drugs were started at the onset of symptoms. CTCAE v 4.02 was used for assessments. Statistical Analysis Used : Changes in scores for sensory, motor and pain symptoms over the study period were compared using repeated measures of General Linear Model of SPSS version 17. Results : 22, 24, 21 and 23 patients were eligible for analysis in four arms. Vitamin E was producing comparable relief as methylcobalamine of peripheral neuropathy. Both vitamin E and methylcobalamine was superior to glutamine and ALC in relieving sensory, motor and pain symptoms. Glutamine and ALC had comparable effects. Conclusions: All four drugs were effective in the alleviation of symptoms with vitamin E and methylcobalaine more effective than glutamine and ALC in control of symptoms of paclitaxel induced peripheral neuropathy.

Evaluation of Protracted Cisplatinum Infusion in Advanced Anaplastic Thyroid Cancer

Introduction: Anaplastic thyroid cancer (ATC) constitutes 1-3% of all thyroid malignancies. Most of the patients of anaplastic thyroid cancer presents with advanced inoperable lesion associated with neck mass dysphagia, and SVC syndrome. At this stage only treatment that can be offered is chemotherapy, as this variety of thyroid cancer does not generally concentrate iodine. Present study evaluates protracted (8 hr) Cisplatinum (CDDP) infusion along with doxorubucin in comparison to conventional (1hr) Cisplatinum + doxorubucin in advanced anaplastic thyroid cancer in terms of tolerance, toxicities and response rates. Methods: 32 previously untreated cases of stage III/IV inoperable anaplastic thyroid cancer were included in the present study. Patients were divided into 2 arms of 16 patients each. Arm I (16 patients) received 1 hr Cisplatin (CDDP) infusion 75mg/m2 + Doxorubicin 60mg/m2 infusion & Arm II (16 patients) received protracted 8 hrs CDDP infusion 75mg/m2+ Doxorubicin 60mg/m2 infusion. All patients were evaluated for tolerance, toxicities and response rate. Results: Arm II patients showed better locoregional response with CR 31.25%, PR 50%, SD 6.25%,PrD. 12.5% as compared to Arm I patients with CR 12.5%, PR 43.75%, SD 18.75%, Pr. D 25%, p= .02. Toxicities like mucositis, nausea & vomiting, diarrhea, nephrotoxicity were also significantly less in Arm II. After completion of 3-4cycles of Induction CT, all patients were treated with External Radiotherapy of 60-66Gy, followed with 2-3 cycles of adjuvant CT. Conclusion: From the present study it can be concluded that protracted cisplatinum infusion along with other chemotherapeutic drugs is an effective and acceptable CT regimen in advanced inoperable thyroid cancer.

MIS3-5 - Fluorodeoxyglucose Positron Emission Tomography for Evaluating Early Response During Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma

ABSTRACT Background To determine whether fluorodeoxyglucose positron emission tomography (FDG-PET) could differentiate between responding and non-responding locally advanced esophageal squamous cell carcinoma (ESCC) early in the course of neoadjuvant chemoradiotherapy (CRT). Methods Patients with T3 or N1M0-1a (AJCC, 6th ed.) ESCC first received a 21-day cycle of induction CT with paclitaxel, cisplatin, 5-FU/leucovorin D 1, 8). This was followed by concurrent paclitaxel, cisplatin CRT (Lin CC et al. Ann Oncol 18: 93; 2007). When the accumulated RT dose reached 40 Gy, the feasibility of esophagectomy was evaluated. In patients for whom esophagectomy was not feasible, CCRT was continued to a dose of 60 Gy. Serial FDG-PETs were carried out before and 14 days after the start of induction CT. Pathologic response (PR) was defined as no or microscopic residual disease. PET response was measured using the standardized uptake value (SUV). Receiver operating characteristic (ROC) analysis was used to evaluate the SUV ability in distinguishing between PR and non-PR. Results Of 65 patients (M:F = 60:5, median age 55, range 39–71) with locally advanced (M0:M1a = 58:7) ESCC enrolled from March 2008 to December 2011, 40 patients underwent esophagectomy and 26 patients were pathologic responders. The median SUV decrease 140 days after the start of therapy was 75.8% for pathologic responders and 30.1% for non-responders (P Conclusions A 35% SUV decrease 14 days after the start of induction CT is significantly associated with PR, but its accuracy in detecting non-responders is too low to justify the clinical use of FDG-PET for early discontinuation of neoadjuvant CRT in patients with locally advanced ESCC.

Customized first-line chemotherapy according to ERCC1 and RRM1 SNPs in advanced NSCLC patients: A phase II study.

e18074 Background: Excision repair cross complementing group 1 (ERCC1) and ribonucleotide reductase1 (RRM1) expression levels are predictive of CT efficacy in some malignancies. “Customized” CT has several advantages: (1) pts are more likely to be treated with agents that they will respond to, (2) pts can be spared the toxicity of agents that they are resistant to, (3) effective treatment can be delivered early in the course of disease. Methods: We planned a phase II multicentric open label study in two steps (based on Simon design) to evaluate ERCC1 SNPs (T118C and C8092A) and RRM1 SNPs (-37C&gt;A and -524T&gt;C) in advanced NSCLC pts. Here we report the first step for futility. Pts received first line CT according to the assessed ERCC1 and RRM1 SNPs status and the correlated expression levels: treatment A (low ERCC1 and low RRM1) Cisplatin plus Gemcitabine; treatment B (low ERCC1 and high RRM1) Cisplatin plus Docetaxel; treatment C (high ERCC1 and low RRM1) Gemcitabine plus Docetaxel; treatment D (high ERCC1 and high RRM1) Docetaxel plus Vinorelbine. Results: 42 pts were enrolled from Jan. 2010 to Oct. 201, 40 pts received at least 1 cycle of CT; median age was 66 yrs (range 47-73); 33 pts were males; 23(55%) pts were ECOG PS 0, 19(45%) PS 1; all pts had stage IV; 23(55%) pts had adenoca, 13(31%) squamous, 6(14%) other types; 25(62%) pts received treatment A, 3(8%) treatment B, 11(27%) treatment C, 1(3%) treatment D. As primary end-point we assessed the overall best response: 18(45%) pts achieved PR, 12(30%) SD, 8(20%) PD, 2(5%) pts were not evaluable. Updated information on OS and PFS will be presented. CT was well tolerated, there were no treatment related deaths. Conclusions: We observed an improved RR in this setting of NSCLC pts treated with CT according to ERCC1 and RRM1 SNPs status. We are planning to continue the second step of this trial (total 110 pts).

Multimodality treatment of pediatric and adult patients with Ewing sarcoma: A single-institution experience.

10082 Background: Treatment of Ewing sarcoma pts. usually follows pediatric protocols, both in children and in adults. However, older patients fare poorly in most series. We analyze our experience with the 2001 protocol of the Spanish Society of Pediatric Oncology. Methods: Retrospective analysis. Schema: 6 cycles (cy) of VIDE chemotherapy (CT: vincristine, ifosfamide, etoposide, doxorrubicin). If no progression, local treatment (surgery or RT) and consolidation adjusted to risk: VACx8 (vincristine, dactinomycin, ciclophosphamyde) in standard-risk pts; if increased risk (axial, complete response in lung metastases or non-pulmonary metastases) VACx1, high-dose CT (busulphan-melphalan) and autologous transplant (ATSP). Analysis: induction CT toxicity, pathological response rates, consolidation treatment, disease-free (DFS) and overall survival (OS) (Kaplan- Meier). Log-rank and Cox regression analysis of prognostic factors in OS. Results: 35 patients (01.2003-05.2011). 60% male. Median age 16 y (r 7-57). Axial (43%), extremities (34%), extra-osseous (18%) and ribs (9%). Metastases: 54% (lung 58%, bone 26%, others 12%). &gt; 1 location: 29%. Induction CT: 83% received 6 cy. 6% early progressions and 3% toxic deaths. 196 cycles of CT. Dose reduction (etoposide) in 60%. Grade 3-4 toxicity: neutropenia 13%, anemia 14%, neutropenic fever 13%, diarrhoea-stomatitis 7%.Local treatment: surgery (49%), radiotherapy (29%), none (22%). In 17 resections, &gt; 90% necrosis in 53%. Consolidation: VACx8 29%; VACx1-ATSP in 34%; 37% other treatments (progression). No ATSP-related mortality. Median follow-up: 36 m ( 5-101 m). Median DFS 25 m (16-34 m). Median OS 28 m (15-41 m), 3-year OS 40%. Median time to progression 7 m (0.4-15 m). Median OS from progression 7 m (0.4-15 m). Age &lt; 15 years, a non-axial primary and no extra-pulmonary metastases were favourable prognostic factors in the univariate analysis. Conclusions: Induction CT with the VIDE regimen is feasible in most patients, with a low risk of early progression. Hematological toxicity is substantial but manageable. Adults patients have a worse prognosis compared to pediatric patients. Unfortunately, survival after progression is dismal.

Treatment of Advanced or Recurrent Cervical Cancer with Cisplatin or Cisplatin Containing Regimens: A Cost Effective Analysis

Background: Trials have demonstrated improvements in survival with adding paclitaxel (P) or topotecan (T) to cisplatin (C) for the treatment of advanced cervical cancer. We sought to evaluate the cost effectiveness of these regimens.Methods: A decision model was developed based on Gynecologic Oncology Group (GOG) protocols 169 and 179. Arm 1 is 6 cycles of cisplatin. Arm 2 is 6 cycles of CP while arm 3 is 6 cycles of CT. Parameters include overall survival (OS), cost and complications. Sensitivity analyses were performed.Results: The incremental cost-effectiveness ratio (ICER) for C versus CP is $13,654/quality-adjusted life-year (QALY) gained. For CT compared to C, the ICER is $152,327/QALY. When compared simultaneously, CT is dominated. At a willingness to pay (WTP) threshold of $50,000/QALY, C is the preferred option but CP is acceptable. Sensitivity analyses suggest that CT would become the preferred option if it was to improve OS to 24 months (compared to 9.4 months).Conclusions: In this model, CP is an acceptable alternative to cisplatin for the treatment of these patients with an increase in cost of only $13,654/QALY. The addition of topotecan did not increase survival enough to justify the increased cost.

Epidemiology of NSCLC in a Costa Rican hospital: 2003-2008.

e12000 Background: Lung cancer has increased in incidence and mortality in the past years. In Costa Rica, the incidence and overall mortality rate of lung cancer is practically the same: 8/100,000 people. Differentiation between squamous and nonsquamous histology is of extreme importance in NSCLC for further molecular investigation and treatment decisions. Epidemiologic differences between histologies have been described where subsets of patients may benefit from a specific treatment approach. There is limited information of NSCLC epidemiology in Latin American populations. This retrospective epidemiologic study analyzed NSCLC in the population treated at Hospital San Juan de Dios (HSJD) in San José, Costa Rica. This is the first study performed in Costa Rica assessing epidemiology and overall survival in NSCLC. Methods: Records of patients diagnosed with NSCLC were obtained from the HSJD from Jan 2003 to Dec 2008. 233 cases were identified, only 89 patients were included in the study. Overall survival (OS) and the relationship between histology, stage, and chemotherapy was analyzed with measurements of position (modes and medians) and Kaplan-Meier method. Results: See table. Additionally, there was no statistically significant difference between histologic subtypes in OS for stage IIIB- IV treated patients. Conclusions: Mortality of NSCLC in Costa Rica is high. Most patients are diagnosed in advanced stages (IIIB-IV). Relatively high percentage of patients were nonsmokers; therefore genetic mutations could play a role in etiology. Squamous cell carcinoma is the most common histology. Cisplatin-paclitaxel improved significantly overall survival independent of histologic subtype. Characteristics of patients diagnosed with NSCLC between 2003 and 2008 in HSJD, Costa Rica (n=89). CI=95% P value Gender (n) Men 58 Women 34 Median age (y) 64.9 Nonsmokers (%) 21 Histology (%) Squamous 42 Adeno 35 LC 11 NOS 12 Stage IIIB-IV (%) 79 4 or + cycles of CT (%) 73 Median OS (m) IIIB With CT 13.3 7.9-18.7 Without CT 2.3 1.5-3.2 p=0.005 IV With CT 8.9 6.8-11.0 Without CT 1.8 0.5-3.1 p=0.025 Adeno With CT 10.2 4.1-17.3 Without CT 2.2 0.7-2.6 Squamous With CT 15.4 4.3-26.5 Without CT 1.3 0.8-1.4 LC With CT 6.5 0.8-12.2 Without CT 0.5 0.3-0.8 NOS With CT 11.3 7.5-15-2 Without CT 1.0 0.4-1.7

B-cell non-Hodgkin lymphomas in childhood: 20 years experience in a single institution.

9569 Background: Our objective was to analyze the clinical and demographic characteristics of children with B-cell lymphoma treated in a single centre in Athens-Greece over the last two decades. Methods: Data were collected by a retrospective review of the charts of all 85 patients (pts) treated to our unit, from 1989 until end of 2009, according to FAB LMB 89, 96 protocols and 2003 modifications. We studied the therapeutic outcome in correlation with their diagnostic group, age at diagnosis, site of disease, response to initial prophase chemo (CT) and status of disease at reevaluation point. Results: 15 pts were excluded due to insufficient data. For the remaining 70 pts the median age was 7.5 years, with a male predominance 3.8:1. According to LMB staging criteria, 6 pts (8.6 %) were classified as Group A, 52 (74.3%) as Group B and 12 (17 %) as Group C all with bone marrow involvement and in 5 combined with CNS involvement. Most of our pts (43/70 – 61.4%) had abdominal tumours, 11 in ENT region, 3 in bones, 4 with cervical disease and 9 had more than one involved sites. 10 of the 58 children of A and B Group (16.3%) were upgraded to Group C due to poor response to initial CT treatment with CycloOncovinPrednizone (COP) or remaining viable tumor at the point of remission assessment after 4 cycles of CT. Regarding outcome 10 pts died (15%), 7 due to progression, 3 due to toxicity, 2 in induction and 1 post autograft. Relapse occurred in 9 children (13%), all with abdominal disease, one of them with concurrent thoracic involvement. Most relapsed patients (7/9) were initially treated as Group B (7/52, 14%), 1 as C and 1 as Group A. The outcome of relapsed children was dismal as 6/9 (67%) died, four initially classified as Group B. Conclusions: In our results, the survival rate is generally excellent (85 %) more than one year off treatment which generally means cure in Burkitt like lymphomas. Children from Group B with unsatisfactory initial response to COP seem to have the worse prognosis.

Is there a place for neoadjuvant chemotherapy in the management of advanced malignant germ cell tumors of ovary?

5079 Background: There is limited data on the role of neoadjuvant chemotherapy (NACT) in advanced malignant ovarian germ cell tumors (MOGCT).We attempted NACT in 20 Pts of advanced MOGCT who were considered high risk for surgery (very poor general health; ECOG performance status, 3-4) in order to preserve fertility. Methods: Between 1988 and December 2009, 20 of 211 patients with MOGCT were considered unsuitable for exploratory laparotomy because of their high risk status. Pts median age was 19 yrs, ranging from 14-28 yrs. All had stage III (n=17) or IV (n=3) disease. Diagnosis was confirmed by FNAC /Biopsy & baseline tumor marker levels. 11 pts had dysgerminoma, 6 had mixed subtype & 3 had endodermal sinus tumor (EST). All were planned for four cycles of BEP chemotherapy followed by fertility sparing surgery (U/L salpingo-oophorectomy + omentectomy ± Lymphadenectomy). Results: 18 Pts were evaluable for treatment response & outcome. One Pt died after 1st cycle of CT due to progressive disease and another Pt was lost to FU after 2 cycles. Post 4 cycles of chemotherapy, 18 responded: CR-13, PR-5. 15 Pts underwent surgery with pathological CR in 13/15 (86.6%); 2 Pts had residual disease, both of them achieved CR following 2 cycles of salvage chemotherapy. Remaining three Pts refused for surgery; 2 out of 3 relapsed at 9 and 12 months, both achieved CR with salvage chemotherapy and subsequent fertility sparing surgery; third Pt continues to be alive and in good health. Currently 18 of 20 patients are alive and disease free and in one status is unknown at a median follow-up of 48 months (range: 12-96 months). All of them have resumed menstruation and 3 eligible Pts have delivered full term healthy babies. Conclusions: NACT followed by fertility sparing surgery is an effective treatment strategy for patients of advanced MOGCT who are high risk candidates for surgery.

Isolated primary extranodal lymphoma of the oral cavity: A series of 15 cases and review of literature from a tertiary care cancer centre in India.

Background:Non-Hodgkin's lymphomas (NHL) have a great tendency to affect organs and tissues that do not ordinarily contain lymphoid cells. Involvement of the oral cavity by NHL is very rare.Materials and Methods:Retrospective analysis was carried out by chart review of patients who presented to our hospital between 1990 and 2008. All those patients whose histopathology at our hospital was confirmed as lymphoma were included.Results:Although we register nearly 2000 new oral cancers every year, most of which are squamous cell cancers, we could trace only 15 cases of oral lymphoma in the last 18 years. Of these, hard palate and alveolus were most common sites (5 each). The median age at presentation was 42.6 years. A vast majority (12/15) were NHL. Most patients (70%) reported with painless progressive swelling without systemic signs, such as fever, weight loss, and so on. Only 2 patients were HIV positive. Nearly two thirds received combinations of CT and RT. Cyclophosphamide, hydroxydaunorubicin, oncovin (vincristine), prednisolone regime was the most common regime offered (12/15). Most of them (67%) had good response to 6 cycles of CT that was followed by RT. 10/15 patients completed treatment. Follow-up data of more than 2 years of follow-up was present in 11/15 patients. With median follow-up of 27 months, 5 were disease free, 5 died, and 1 controlled following 2nd line of CT, 2 were lost to follow-up and 2 were alive with disease.Discussion:Head and neck lymphoma is the second most common region for extranodal lymphoma. The nasopharynx, tonsils, and base tongue are most often involved. Unlike the western world, oral cavity involvement is extremely rare. Interestingly, only 2 patients tested positive for HIV and most were young patients. Oral lymphoma may mimic benign oral conditions that often lead to misdiagnosis.Conclusion:Although oral cavity may be the preferred site of NHL in immunocompromised patients it does occur in immunocompetent patients as well. Isolated oral lymphoma is extremely rare and from our data we can say that oral NHL in Indian sub population is more aggressive compared with western literature.

A phase III protocol of androgen suppression (AS) and radiation therapy (RT) versus AS and RT followed by chemotherapy with paclitaxel, estramustine, and etoposide (TEE) for localized, high-risk, prostate cancer, RTOG 9902.

4632 Background: High-risk, localized prostate cancer (PCa) is generally treated with a combination of RT and long-term AS. It was our hypothesis that adjuvant CT would improve the survival rate of high-risk PCa when used in combination with RT and AS. Methods: Pts with PSA 20-100 and Gleason score (GS) ≥7 or clinical stage ≥T2 and GS ≥8 were randomized to RT and AS with or without four 21-day cycles of CT, starting 28 days after RT, with oral estramustine 280 mg tid × 14 days, oral VP-16 50 mg/m2 in divided doses bid × 14 days, and paclitaxel 135 mg/m2 iv on day 2. Warfarin was originally given at 1 mg/day during CT, but, after thromboembolic (TE) toxicity was observed, the dosage was increased to keep the INR between 1.5 and 2.5. RT consisted of 46.8 Gy to a small pelvic field followed by a prostate boost of 23.4 Gy for a total of 70.2 Gy. AS consisted of LHRH for 24 mos beginning 2 mos preRT plus oral antiandrogen before and during RT. Results: This study opened in Jan 2000 and closed in Oct 2004 with a total of 397 pts (of a planned 1,440) entered (380 eligible). We previously reported on the TE toxicities that led to early protocol closure (Rosenthal, et al. IJROBP 73:672, 2009), but pts have been followed for the primary endpoint, and we report now overall survival (OS) as well as biochemical failure (BF). Pts had high-risk features: 68% had GS ≥8, median PSA was 24.2, and 33% were cT3. Median FU is 6 yrs. 5-yr OS was 86% for both the RT+AS and RT+AS+CT arms (p=0.79). 5-yr BF rates were also similar: 43% for RT+AS and 48% for RT+AS+CT (p=0.26). Conclusions: RTOG 9902 failed to reach its accrual goal due to toxicity. With 5-yr data, there is no difference in OS observed with the addition of adjuvant CT. No difference in 5 yr BF rates was noted. Sample size reduction because of premature closure may have reduced the ability to detect a significant difference. A similarly designed trial, RTOG 0521, completed accrual in 2009, but CT was delivered with docetaxel/prednisone rather than TEE. Results of RTOG 0521 are pending and may help better define the role for adjuvant CT for high risk, localized PCa pts. Supported by NCI grants U10 CA21661 and U10 CA37422. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Bristol-Myers Squibb, Ferring Pharmaceuticals, Watson Pharmaceuticals Bristol-Myers Squibb

TARC Is Useful as Additional Prognostic Factor for Hodgkin's Lymphoma Outcome.

Abstract 1557Poster Board I-580 IntroductionThe CC thymus and activation related chemokine TARC, a protein highly expressed by Reed-Sternberg cells and in the microenvironment of Hodgkin's lymphoma (HL) involved lymph nodes, as well as detectable in the serum of HL patients (pts), has been reported to have prognostic value in retrospective analysis. The aim of our study was to prospectively investigate the association among PET-2 results and TARC serum levels (T) in HL and the prognostic role of T in disease relapse or progression. Patients and MethodsBetween November 2006 and June 2009, T was measured by ELISA in 73 pts: 50 newly diagnosed untreated pts (Group U) and 23 pts relapsing or progressing after first line CT±RT (Group S). Group U pts received stage-directed therapy consisting in 4 ABVD cycles followed by IFRT for stage I-II A, and 6-8 ABVD cycles ± RT on bulky sites of disease for stage II B, III-IV. Group S pts received cytoreductive CT with Ifosfamide-containing regimens followed by HDBEAM+ASCT. T evaluation was repeated after each CT cycle, at the end of treatment and during follow-up. ResultsMain pts characteristics were as follows: males/females: 32/41; age<45/≥45yrs: 59/16; Nodular Sclerosis (NS) histology/other: 54/73; stage I+II/III+IV: 46/27; B symptoms: 37; bulky disease: 35; nodal/extra±nodal involvement: 49/24; >3/≤3 involved sites: 34/39; IPS>2/≤2: 8/65. Basal T (T0) (median, IQ range) was significantly higher in Group U vs S (23540, 6528-50710 vs 1448, 735-8278; Mann-Whitney test P=0.002); T0 values >536 were observed in 43 (86%) Group U pts and 18 (78%) Group S pts (536 was the 95th centile of T distribution in a group of 40 independent healthy subjects). Pts with NS, bulky disease and extranodal involvement had significantly higher T0 levels than their counterparts. After 2 CT cycles, T (T2) was significantly lower than T0 in Group U (Wilcoxon paired sample test P<0.001), but not in Group S pts (p=0.090); T2 values >536 were observed in 18 (36%) Group U pts and 14 (61%) Group S pts. PET-2 scan was positive in 20 pts (27%) (Group U: 18%, Group S: 48%); PET- 2 was positive in 19/61 pts (31%) with T0 >536 and in 1/12 pts (8%) with T0 ≤ 536; in 17/32 (53%) pts with T2 >536 and in 2/35 (6%) pts with T2 ≤ 536. The chance of having a positive PET-2 was similar in pts with T0 >536 and T2 ≤ 536 compared with pts with T0 ≤ 536 (OR: 1.1; 95% CI: 0.9-13.5), whereas it was 13-fold greater in pts with both T0 and T2 >536 (OR: 12.6; 95% CI 1.4-110). Median follow-up was 18 months (interquartile range: 13-25 months); 13 (18%) pts had relapse or progression (7 Group U, 6 Group S), 24-months progression-free survival (PFS) was 83.4% in Group U and 60.6% in Group S. PFS was 100% vs 78.6% vs 59.4% in pts with T0 ≤ 536, T0 >536 and T2 ≤ 563, and both T0 and T2 >536, respectively. ConclusionsOur study confirms that HL pts have increased serum TARC values at baseline compared with healthy subjects; moreover T0 combined with values observed after 2 cycles of CT may have a role in predicting PET-2 results and disease outcome. DisclosuresNo relevant conflicts of interest to declare.

Vinorelbine and fluorouracil plus leucovorin combination (ViFL) in patients with anthracycline and taxane-pretreated metastatic breast cancer: a phase II study

This phase II study was designed in order to evaluate efficacy and safety of the combination of vinorelbine (VNB), fluorouracil (FU) and leucovorin (LV) in patients with metastatic breast carcinoma (MBC) previously treated with anthracyclines and taxanes. From 12/2003 to 12/2007, 51 women (median age 59) were treated. Performance status (PS) (ECOG) was 0-2 (median 0). The chemotherapy consisted of VNB 25 mg/sqm on day 1 added to FU and LV (following De Gramont schedule) on day 1 and 2. Treatment was repeated every 14 days. 518 cycles of CT were administered (median 12). Most common sites of metastatic spread were: bone, liver, lymph nodes, lung. We recorded three cases of G4 neuthropenia and in one case it was febrile; no others G4 toxicities were seen. G3 toxicities were more common, especially neuthropenia (8 patients) asthenia (4) mucositis (2) and Hand-Foot Syndrome (2). Overall response rate was 27.5% (14 patients had a PR) and disease control rate was 76.5%; 12 patients experienced disease progression. Median time to progression (TTP) was 7.70 months and overall survival (OS) was 18.70 months. Results demonstrate that the ViFL regimen has substantial activity in patients with MBC already treated with anthracyclines and taxanes. The combination may be considered a valid choice for the treatment of MBC. Better survival results were seen in patients with visceral metastases than bone involvement. The low response rate shows that the ViFL regimen is not suitable for the neoadjuvant setting.