No abstract

5515 Background: we have previously reported that ICT plus CRT is more active than CRT alone in pts with unresectable LAHNC (Hitt et al: ASCO 2005, abstract 5578). Here we present new data of efficacy and time to progression (TTP) in this trial. Methods: Patients: eligible pts included those with unresectable LAHNC, measurable disease, adequate organ function and ECOG 0–1. Pts were stratified according to primary tumor site. Treatment: Induction chemotherapy regimens (3 cycles): PF : P 100 mg/m2 day (d) 1, then F 1000 mg/m2 c.i. d1–5 q 21d; TPF: T 75 mg/m2 d1, P 75 mg/m2 d1, F 750 mg/m2 c.i. d 1–5 q 21 d plus G-CSF and ciprofloxacin. Chemoradiotherapy: conventional RT up to 70 Gy plus P 100 mg/m2 d 1–22–43 Results: Patients: a total of 310 pts have been accrued. Pts/tumor characteristics (ECOG, age, primary site, T/N stage) were well balanced among the three arms. T/N stage: T3–4 (88%); N2–3 (63%); pharynx-oropharynx site (62%). Treatment: Median number of cycles of ICT: 3; median dose of RT: 70 Gy, median number of cycles of P during RT in three arms: 3. Efficacy: Complete Response: 70% (ICT + CRT) vs. 49% (CRT alone) (p = 0.01). The response rate was similar between TPF and PF. Time to progression (TTP) in months: 16 (TPF + CRT); 12 (PF + CRT) vs 8 (CRT alone) (log-Rank= 0.02). G 3/4 toxicity (NCI criteria): Febrile neutropenia: 21% (TPF); mucositis: 10% (PF). Mucositis was observed in 55% (TPF + CRT), 60% (PF + CRT) and 36% (CRT alone) of the pts, respectively Conclusions: The results of the present randomised clinical trial demonstrate that the combination of ICT + CRT significantly increases the complete response rate and prolongs TTP when compared to CRT alone in patients with unresectable LAHNC. No significant financial relationships to disclose.

Skeletal muscle mitochondria remain histologically and functionally unaffected in PMR and in GCA.

We review the current status of the conventional therapeutical approaches of cervix carcinoma. Radical hysterectomy remains as the main stone in early stages and play an important role in relapses. Radiotherapy plays an important role in early and advance disease. New techniques and image expand indications and treatment possibilities. Chemotherapy platinum based with radiation therapy goes on being the standard treatment in advanced tumours or non surgical candidates. New systemic strategies are being explored in clinical trials.

5019 Background: In prostate cancer, expression of survivin, a protein that inhibits apoptosis, is associated with resistance to taxanes and poor outcome. LY2181308 reduces survivin expression and consequently is expected to improve activity of taxanes, such as docetaxel. A randomized phase II study was conducted to assess the activity of the combination. Methods: Adult patients (pts) with CRPC, ECOG performance status <2, and no bone or CNSmetastases were randomized 1:2 to standard docetaxel/prednisone every 21 days (Arm A) or standard therapy combined with LY2181308 given as a 3-hr IV infusion (Arm B). Analysis was planned and performed after 130 pts progressed or died. This assessment provided a 70% chance of detecting a difference in progression-free survival (PFS) at the 10% significance level. Initially, LY2181308 was given as a loading dose (3 consecutive days) and then as a weekly 3-hr IV maintenance dose. Arm B also included a window treatment with LY2181308 monotherapy equivalent to a 21-day cycle of docetaxel before starting combined treatment. The primary endpoint was PFS. Results: This study enrolled 154 pts. The median PFS for Arm B was 8.64 (90% CI, 7.39–10.45) months vs. 9.00 (90% CI, 7.00–10.09) months in Arm A, showing no statistical difference (log rank p=0.755). The median overall survival (OS) for Arm B was 27.04 (90% CI, 19.94–33.41) months vs. 29.04 (90% CI, 20.11–39.26) months for Arm A (log-rank p= 0.838). The PSA responses (>50% reduction in PSA) were similar: 56.9% for Arm A and 56.1% in Arm B (p=0.856). Most pts had no pain or mild pain at baseline and during the active period. Pts treated in Arm B had a higher frequency of serious and nonserious adverse events (AEs) than those in Arm A. The observed AE and pharmacokinetic (PK) profiles were consistent with the known safety and PK profiles of LY2181308 and docetaxel. Conclusions: The addition of LY2181308 to a standard docetaxel/prednisone regimen showed no improvement in PFS, PSA response, and OS in first line CRPC pts. The safety profile of docetaxel and LY2181308 is predictable and consistent with the known safety profiles. Clinical trial information: NCT00642018.