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Summary Background Cisplatin and paclitaxel are active in cervical cancer and both are able to potentiate the effects of radiotherapy. In this study we evaluated the maximum-tolerated dose (MTD) of paclitaxel in combination with a fixed dose of cisplatin when given weekly concurrently with pelvic radiotherapy to patients with carcinoma of the cervix uteri. Patients and methods Eighteen patients with cervical cancer were enrolled in this study. Cisplatin (30 mg/m2) and paclitaxel (starting dose 40 mg/m2; 5 mg/m2 escalation per level) were given on day 1 of radiotherapy and then weekly for six times. Radiotherapy was given to the pelvis with a four-field box technique for five days each week. Patients received 65 Gy in 1.8 Gy fractions. Cohorts of three patients were enrolled at each level and three further patients were included if one or two dose-limiting severe adverse events (SAE) were recorded. SAE was defined as grade 3 or 4 nonhematologic toxicity, excluding nausea or vomiting and alopecia, grade 4 neutropenia or thrombocytopenia, and prolonged (> 1 week) neutropenia or thrombocytopenia. Results Four levels were studied (paclitaxel 40, 45, 50, 55 mg/m2) with three, five, four and six patients enrolled, respectively. The MTD of paclitaxel was found at 50 mg/m2/wk and cisplatin 30 mg/m2/wk. Diarrhea was the dose-limiting toxicity. Thirteen patients were evaluable for response: seven complete and five partial responses were obtained with an overall response rate of 92.3%. Conclusions The MTD of paclitaxel is 50 mg/m2/wk when associated to cisplatin 30 mg/m2/wk and concurrent pelvic radiotherapy. Diarrhea is the dose limiting side effect. Preliminary data suggest that concurrent chemoradiotherapy with paclitaxel and cisplatin could be a very active treatment for patients with locally advancedcarcinoma of the cervix.

Background Actual tolerability of sunitinib is still poorly documented in elderly patients with metastatic renal cell carcinoma (mRCC). Patients and methods Charts of elderly patients treated with sunitinib for mRCC were reviewed in six Italian centers to assess safety (primary objective), efficacy and correlation of toxicity with comprehensive geriatric assessment (CGA) (secondary objectives). Results Sixty-eight patients were eligible, and the median age was 74 years. CGA was carried out in 34 patients (41% fit, 41% vulnerable and 18.5% frail). The dose reduction to 37.5 mg was made upfront or soon after the first cycle in 69.1%. More frequent toxic effects were fatigue (80.9%), mucositis (61.8%) and hypertension (58.8%). Cardiac events occurred in nine patients. In 10 patients, therapy was interrupted early due to rapidly progressive disease (10.3%) or severe toxicity (4.4%: 1 cardiac failure, 1 fatigue, 1 febrile neutropenia). At a median follow-up of 27.1 months, the median OS was 18.3 months and the median PFS was 13.6 months. Correlation was not found between frailty at CGA with severe toxicity nor with response. Conclusions Treatment with sunitinib is effective in elderly patients; yet early interruptions were frequent. Starting treatment at reduced dose and escalating in the absence of severe toxicity could be suggested.

Background A large international phase III randomized trial (TIGER study) has been recently planned to compare the TI-CE multi-cycle high-dose chemotherapy (HDCT) with standard chemotherapy as salvage treatment for patients with relapsed germ cell tumors (GCT), but to date there are no reported experiences with this regimen other than the phase 2 study from MSKCC (Feldman et al – JCO 2010). We present preliminary results of our experience with TI-CE in relapsed/refractory GCT patients. Methods From August 2009 to April 2012, patients with relapsed/refractory GCT received TI-CE comprising a mobilizing phase with paclitaxel and ifosfamide (TI) with leukapheresis of peripheral blood progenitor cells (PBPCs), followed by 3 HDCT courses with CE (carboplatin AUC 21 and etoposide 1200 mg/m2), with PBPC reinfusion. Biosimilar filgrastim (Zarzio®) was used in the HDCT phase for all patients after PBPC reinfusion. Results 26 patients (25 males, median age 34) started on TI, but 3 of them did not receive CE: two had rapidly progressive symptomatic brain metastases, the third one refused HDCT. Of 23 patients, 20 completed the TI-CE regimen and are evaluable, while 3 are still receiving treatment. There were no treatment-related deaths. The median number of days from the start of CE until recovery of neutrophils to 1,000/mm3 was 14. Twelve (60%) of the 20 evaluable patients achieved a complete remission (CR) (5 clinical CR, 5 pathological CR, 2 surgical CR), 5 had marker-negative partial remissions lasting 2, 2 + , 2 + , 6+ and 21+ months, and 3 progressed. After a median follow-up of 13 months (range, 2 to 33+), 15 (75%) evaluable patients are continuously progression-free. Of 4 mediastinal primary nonseminomatous GCT, 2 achieved a CR (1 sCR and 1 pCR) lasting 7 and 12+ months, respectively. Conclusions Our experience confirms that the TI-CE regimen is safe and active, with a response rate and a recovery time of neutrophils after CE similar to that reported in the MSKCC study. Updated results will be presented at the meeting. Disclosure All authors have declared no conflicts of interest.

More than 50% of lung cancer patients are diagnosed over the age of 65 and about 30% over 70. Small-cell lung cancer (SCLC) accounts for 20–25% of lung carcinomas. Chemotherapy is the cornerstone of treatment for SCLC. Usually in the elderly it is difficult to administer the same chemotherapy administered to younger patients because elderly patients tolerate chemotherapy poorly. The empirical reduction of drug doses may be criticized. The best approach is to design specific trials in order to develop active and well-tolerated chemotherapy regimens for SCLC elderly patients. The standard therapy in limited disease is combined chemo-radiotherapy followed by prophylactic brain irradiation for patients achieving a complete response. In the elderly, the addition of radiotherapy to chemotherapy must be accurately evaluated, considering the slight survival improvement and the potential relevant toxicity.

In the past 20 years, a number of studies have investigated the relationship between sex hormones and liver cancer. Experimental studies indicate that a dynamic process, with sequential modifications in the pattern of sex hormones in the serum and of sex hormone receptors in the liver, occurs progressively during hepatocarcinogenesis. Overall, it seems that both androgens and oestrogens may enhance liver carcinogenesis, while androgens may also support the growth of established liver tumours. Unfortunately, clinical studies of endocrine treatment of hepatocellular carcinoma (HCC) have not adequately tested the suggestions from biological studies. So far, no clinical trial has been performed to test the efficacy of endocrine manipulation for the chemoprevention of HCC in cirrhotic patients nor in preventing relapse after radical resection of primary HCC. Anti-oestrogens have been the most studied agents for the endocrine treatment of established HCC, although the rationale that supports their use is weaker than for anti-androgens. Studies with anti-androgens have produced prevalently negative results, due to either a lack of activity or excessive toxicity. The use of chemical castration, which theoretically could enhance the activity of antihormonal compounds, yielded no benefit at all. In summary, there is, as yet, no definitive evidence that endocrine treatment favourably affects the outcome of patients with HCC.

Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progression-free survival (PFS) per central review based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success). Results In EVE + BEV (n = 182) and IFN + BEV (n = 183) arms, median age was 60/60 years, 76/72% of pts were men, MSKCC risk was favourable/intermediate/poor in 36/57/7% and 36/57/7% of pts, and 43/46% of pts had >2 organs involved, respectively. For EVE + BEV and IFN + BEV, median treatment duration was 8.5/8.3 months, respectively; 23/26% of pts discontinued due to AEs. In EVE + BEV and IFN + BEV arms, median PFS by central review was 9.3/10.0 months (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P =0.485), respectively; probability of subsequent phase III success was 5.1%. Results of central and local PFS analysis were consistent. Objective response rate was 27/28% in EVE + BEV and IFN + BEV arms, respectively. Median overall survival (OS) was not reached in the EVE + BEV arm and was 25.9 months (95% CI: 21.1, 30.2) in the IFN + BEV arm. Most frequent AEs (%) were stomatitis (63), proteinuria (49), diarrhoea (39), hypertension (38), and epistaxis (35) in EVE + BEV arm and decreased appetite (45), fatigue (41), proteinuria (37), and pyrexia (35) in IFN + BEV arm. Conclusions In RECORD-2, PFS and tolerability were similar for first-line EVE + BEV and IFN + BEV. Final OS analysis will occur after 2-year follow-up. Disclosure A. Ravaud: Alain Ravaud is a member of global, European, and/or French boards on urological tumors for Pfizer, Novartis, GlaxoSmithKline, Bayer-Schering, and Dendreon, and has received institutional grant support from Pfizer, Novartis, and Roche. O. Anak: Ozlem Anak is an employee of Novartis Pharma AG. D. Pelov: Diana Pelov is an employee of Novartis Pharmaceuticals Corporation. A. Louveau: Anne-Laure Louveau is an employee of Novartis Pharma S.A.S. T. M-H: Tay M-H is a speaker for an advisory board for Novartis Pharmaceuticals Corporation. B. Melichar: Bohuslav Melichar has received honoraria from Novartis and Roche and served on an advisory board for Roche. All other authors have declared no conflicts of interest.

15012 Background: CP every 3 weeks is the standard for pts with OC, but elderly pts frequently receive modified schedules or single agent chemotherapy to avoid toxicity. A prospective phase 2 study was conducted to describe tolerability and activity of a weekly schedule of CP in elderly pts with OC. Methods: Pts aged ≥70 years with chemo-naive OC, stage IC-IV, ECOG PS≤2 were eligible. Treatment was C (AUC 2) + P (60 mg/m2) on days 1, 8, 15 every 4 weeks, up to 6 cycles. A 2-stage minimax design was applied. With rate of pts without unacceptable toxicity in the first 3 cycles (UT) as primary endpoint, alpha 0.05 and beta 0.10, p0=0.75, p1=0.95, ≥23/26 pts without UT were required at the final stage. Toxicity was coded with NCI-CTC and response by RECIST. Geriatric assessment was performed by ADL (Activities of Daily Living) and IADL (Instrumental ADL). Results: 26 pts were enrolled. Median age was 77 (range 70–84). PS0: 10 pts, PS1: 16 pts. 14 pts (53.8%) had ≥2 comorbidities. 32%/72% had some ADL/ IADL dependency, respectively. 23 pts (88.5%) did not suffer UT. The 3 UT recorded were g3 heart rhythm (1 pt), g3 liver (1 pt), prolonged haematological toxicity (1 pt). Other main toxicities: g3 thrombocytopenia 1 pt, g2 constipation 2 pts (8%), g1 neuropathy 4 pts (15%). Out of 13 pts with at least one measurable lesion, 4 partial responses were observed (response rate 30.8%, 95% exact CI: 9.1–61.4). Out of 6 pts with non-measurable disease and 2 pts evaluable only for Ca125, 4 complete responses were observed (50%). Conclusions: In this series of elderly OC pts, characterized by a high incidence of comorbidities and functional impairment, weekly CP has a favourable toxicity profile. In this setting, a comparison of weekly vs 3-weekly CP is advisable to compare efficacy. No significant financial relationships to disclose.