Raltitrexed (tomudex) administration in patients failing multiple prior chemotherapy regimens in advanced colorectal cancer: a pilot study.
OBJECTIVE
To evaluate efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) failing multiple prior chemotherapy regimens (e.g. 5-FU+LV, CPT-11, etc).


METHODS
20 patients with ACC; 13 males/7 females, median age 64 (range: 53-69), median Karnovsky PS: 80 (70-90), and sites of metastases; liver: 16, lung: 6, lymph nodes: 9, peritoneal: 8 and a life expectancy of at least 3 months, were entered in the present pilot study of Raltitrexed administration. All patients had progressed after prior chemotherapy with 5-FU+LV and subsequently CPT-11, and some had received further infusional 5-FU, Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days.


RESULTS
3 patients obtained stable disease (SID), 15%, with tumor marker decline (CEA, CA-19.9). Time-to-progression was 4.8 months (2.2-7) and survival 7.4 months (6.0-7.8). Toxicity was in general not severe and consisted mainly of myelosuppression; neutropenia (WHO) grade 2: 45% and grade 3: 22%, and anemia grade 1-2: 40%.


CONCLUSIONS
Response to treatment with Raltitrexed is limited in patients with ACC failing multiple prior chemotherapy regimens, however, a limited percentage of patients with SD derived clinical benefit.
Tsavaris
N
N
Department of Pathophysiology, Laikon General Hospital, Athens University School of Medicine, Greece. tsavari1@otenet.gr
Kosmas
C
C
Vadiaka
M
M
Kontos
A
A
Fotia
M
M
Angelopoulou
A
A
Vrizidis
N
N
Soulla
M
M
Sougioultzis
S
S
Koufos
Ch
Ch
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use* / Q000633:toxicity; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010865:Pilot Projects; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D011799:Quinazolines; D013876:Thiophenes; D013940:Thymidylate Synthase; C068874:raltitrexed