{'fraction_non_alphanumeric': 0.04712279111916629, 'fraction_numerical': 0.045310376076121435, 'mean_word_length': 4.478908188585608, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Interleukin-2 (IL-2) with 13-cis retinoic acid (RA) to prolong disease free and overall survival in metastatic colorectal cancer.

3629 Background: In a phase 1B study we established that low-dose IL-2 and 13-cis retinoic acid was not toxic and could be administered safely as maintenance therapy for patients (PTS) exhibiting response or disease stabilization to chemotherapy, but at a high risk of relapse (Clin Cancer Res 7: 1251-1257, 2001). A phase II study (Int J Oncol 20: 1275-82, 2002) showed the efficacy of such regimen in improving immunological parameters and in prolonging response in the same category of PTS. The objective of this phase II study was to verify whether the combination of IL-2 and RA could improve the outcome of PTS operated for colorectal cancer recurrence.


METHODS
20 PTS (median age 66 years, 55% males, performance status 0-65%, 1-35%) were treated from September1998 to September 2001. Eight PTS had synchronous metastases, while 12 had a median disease-free survival of 14 months and had received a 5-fluorouracil (5-FU) leucovorin (LV) based adjuvant chemotherapy. After curative resection of metastases, PTS were treated for 6 months with oxaliplatin/5-FU/LV. After chemotherapy PTS received IL-2, 1.8 x 106 I.U. plus RA 0.5 mg/Kg for 5 days/week for 2 consecutive cycles of 3 weeks, with a 1-week rest, for up to 3 years. PTS were monitored every 2 months by determination of vascular endothelial growth factor (VEGF), CD4/CD8 ratio, NK and tumor markers, with response assessed every 4 months.


RESULTS
The toxicity of IL-2 and RA was low. With a combination of surgery and chemotherapy, a 75% response rate was obtained (95% C.I., 51%-91%). After a median follow-up of 20 months, median time to progression and overall survival were not reached yet. The 5-year survival rate was 52%. There was an improvement of all immunological parameters controlled over time (CD4/CD8, NK, decrease of VEGF).


CONCLUSIONS
Compared to historical controls, IL-2 and RA therapy improves the DFS and overall survival after curative resection of metastases from colorectal cancer. A phase III randomized trial has been started. No significant financial relationships to disclose.