We evaluated the antitumoral efficacy and safety of CPT-11 125 mg/m2 (weekly 90 min i.v. infusion; days 1, 8 and 15) combined with UFT (oral combination of tegafur and uracil) 200 mg/m2/day plus leucovorin (LV) 45 mg/m2/day (both divided into three separate oral doses every 8 h, days 1-21) every 4 weeks as first-line chemotherapy of metastatic colorectal cancer (CRC). Fifty-three patients > or =18 years old with histologically confirmed diagnosis of advanced CRC and bidimensionally measurable disease were enrolled. Three patients (6%) showed CR and 8 patients (15%) showed PR (ORR = 21% (95% CI, 10-32). Stable disease was reported in 19 patients (36%) [tumor control rate = 57% (95% CI, 43-70)]. The median time to progression and overall survival were 7.9 and 18.2 months, respectively (1-year rate = 74%; 2-years rate = 26%). CPT-11/UFT/LV treatment was well tolerated: the most reported grade 3/4 toxicities were neutropenia (11% of patients) and delayed diarrhea (28% of patients). No significant differences in response rate, survival or toxicity were found between younger (< or =65 years) and older patients (> 65 years). Weekly CPT-11 plus UFT/LV was found effective and safe as first-line chemotherapy for metastatic CRC. The addition of CPT-11 to UFT/LV doubled the response rate compared to the results previously reported with UFT/LV, while myelosuppression remained low.

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BACKGROUND: Bortezomib is an useful drug for the second line treatment of Multiple Myeloma (MM). This reversible proteasome inhibitor obtains durable responses in relapsed or refractory MM, given as monotherapy or in combination, with acceptable toxicity. AIM: To analyse the overall response of bortezomib plus dexamethasone in patients with relapsed or refractory MM after treatment with vincristine, adriamycin and dexamethasone (VAD) regimens. The time to progression (TTP), time to alternative treatment (TTAT), overall survival (OS) and toxicity profile were also studied. PATIENTS AND METHODS: We conducted a retrospective study of 58 patients with relapsed or refractory MM from seven Andalusian hospitals since March 2005 until June 2008. Patients received bortezomib and dexamethasone as second line therapy after a prior treatment with VAD regimens. The patients were treated with standard bortezomib dose (1.3 mg/m2 IV bolus on days 1, 4, 8 and 11) plus dexamethasone (40 mg/d PO the same days) every 21 days, for up to 8 cycles. The mean age of our series was 57 years (range 39–66) and included 53% males. The prognostic variables at the time of diagnosis were: beta2-microglobuline &gt;3,5 mg/l (57 %), albumine &lt;3,5 g/dl (41%), mean of plasma cells in bone marrow (37 ± 3,6%) and ISS stages at diagnosis (stage I 29%, stage II 28% and stage III 43%). The incidence of plasmacytoma was 22%. Response was evaluated according to the modified EBMT criteria after 4th and 8th courses. Adverse events were graded based on WHO toxicity scale. RESULTS: Fifty-eight patients with refractory/relapsed MM after VAD were analysed with a median follow-up of 11.6 months (1.5–40.5). Forty-eight patients (83%) were evaluated after 4 cycles and the overall response (OR), considered as partial response (PR) or better, was 70.9%; complete response (CR) 18.8%; near complete response (CnR) 18.8%; PR 33.3%; minimal response (MR) 2.1%; stable disease (SD) 12.5% and progression 8.3%. Thirty-three patients (57%) received 8 cycles and the analysis showed the following responses: OR 63.7%, CR 9.1%, CnR 27.3%, PR 27.3%, SD 6.1% and progression 12.1%. In patients who progressed, the median of TTP was 9 months (4–20) and the median of TTAT was 9 months (5–22). Grade 3–4 anemia, neutropenia and gastrointestinal toxicity were not observed in our series. Thrombocytopenia and neuropathy (grade 3–4) appeared in 3% and 11% respectively. Thirty percent of patients required dose reduction of bortezomib whereas dexamethasone was ajusted in 11% of patients, because of toxicity or intolerance. The overall survival of the series was 76%. CONCLUSION: The combination of bortezomib and dexamethasone is an effective alternative of second line treatment without severe toxicity in patients with refractory/relapsed Multiple Mieloma.

2690 Poster Board II-666 Background Despite of all the strategies carried out in the management of Follicular Lymphoma (FL), this disease has remained incurable, and still none of the schedules tested in newly diagnosed patients has yielded a “standard” front-line regimen for FL. The synergistic association of Fludarabine-Cyclophosphamyde (FC) is known as one of the most active regimens for FL, and the addition of Rituximab (R) has improved the efficacy of FCR combination. However, the associated severe myelosuppression when this regimen is administered at standard doses has clearly limited a more extended use. Therefore, different low-intensity schedules have been tested in order to decrease toxicity. The availability of oral F has allowed a more adequate outpatient management of FCR regimen, with expected similar efficacy as the standard intravenous administration. Oral FCR would carry a better compliance and quality of life during treatment, and of course lower hospital expenses. Aims 1) To evaluate efficacy and safety of a lower intensity FCR in first-line for FL. 2) To assess the potential advantages in efficacy and toxicity profile of the oral versus intravenous administration. Methods Follicular lymphoma (WHO histological grades 1-2) patients (pts) aged = 18, previously untreated, WHO-PS= 2, = 2-fold renal and hepatic function values were eligible. Outpatient treatment: Intravenous FC/ FCR (iv): Fludarabine (F) 25 mg/m2/d plus Cyclophosphamyde (C) 250 mg/m2/d (d 1-3), Rituximab (R) 375 mg/m2 (d1) × 4 28-day cycles; Oral FCR (po): F 30 mg/m2/d plus C 175 mg/m2/d (d 1-3), R 375 mg/m2/ (d1) × 4-6 28-day cycles. Stages III-IV and FLIPI= 3 patients at diagnosis achieving CR1 received R maintenance: R 375 mg/m2 q/3 months x 8 doses. Toxicity was recorded at every cycle and thereafter during follow-up, and classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Results From march 1999 to august 2009, 92 pts were prospectively included: M age: 57 (32–81), M:F 44:48, Stages III-IV: 81 (88%), B-symptoms: 29.3%, FLIPI= 3: 36 (39.1%). BM and PB involvement: 52 (56.5%) and 31 (33.7%) respectively. Bcl-2 rearrangement by PCR and/or FISH: 46 (50%). Thirty-seven (40.3%) pts received FC or FCR iv; 55 (59.7%) FCR po. M number of cycles: 4 (3-4) FC/FCRiv; 6 (3-6) FCRpo. Eighty-six pts were evaluable for response: ORR rates FCRiv versus FCRpo: 89.2% vs 100% (p=0.03); CR rate FCRiv versus FCRpo: 54% vs 70.9% (p=0.01). Regarding grades 3-4 (g3-4) toxicity, neutropenia was the most frequent and limiting AE: 53/86 pts presented neutropenia g3-4: 21 (56.7%) and 32 (65.3%) in FCRiv and FCRpo respectively (p=0.02). However, infection rate was 35.1% in FCRiv and 30% in FCRpo (NSD), with a tendency to a higher severity and even causing 1 death FCRiv (NSD). Grade 3-4 thrombocytopenia occurred in 7 FCRiv and 1 FCRpo pts (p=0.03), with severe hemorrhage in 2 FCRiv pts (1 subaracnoid and 1 intestinal in a patient with colon angiodysplasia), and anemia g3-4 in 5 FCRiv and 1 FCRpo (p=0.02). Liver toxicity occurred only with g1-2, and no renal toxicity at all was observed. Fifty-three pts received R-Maintenance: FCRiv: 25/37 (67.5%), FCRpo: 28/49 (57.1%). Withdrawal of R-maintenance occurred in 21 pts (12 FCRiv; 9 FCRpo) due to neutropenia and mild but recurring infections in 18 (85.7%) and in 3 pts due to progression. Four pts relapsed with a M TTP: 13 m (9–48); and 3 pts died (1 infection, 2 progression). Transformation to aggressive NHL occurred in 2 pts, and 1 patient was diagnosed with AML/MDS 4 years after ASCT. With a MFU: 25.7 m (0.3–119.4), overall survival (OS) was 95.4% (IC 95% = 9.3–100%), mean OS= 114.6 m (IC95% 109.3–119.9) and event-free survival (EFS) -considering progression, relapse or death- was 85.3% (IC95% 73.7–96.8%), mean EFS= 106.2 m (IC95% 96.6–115.8 m. No significant differences were found between oral and iv FCR. Conclusions 1) Low-dose FCR is a potent first-line and safe regimen for FL (including pts> 60 yo), with very high ORR and CR rates. Oral low-dose FCR shows better results (ORR and CR) than FCRiv in our series. 2) Although neutropenia remains the major concern with this regimen, oral FCR is associated to a lower incidence of mild and severe infections. Oral low-dose FCR appears as an effective outpatient treatment for untreated FL, with manageable toxicity. Disclosures: No relevant conflicts of interest to declare.