A phase II trial of raltitrexed (Tomudex) in advanced pancreatic and biliary carcinoma.
OBJECTIVE
To evaluate the impact of raltitrexed (Tomudex) on the quality of life in a multicenter, phase II study in advanced pancreatic and biliary carcinomas.


METHODS
Forty-six patients with advanced, histologically proven pancreatic (n = 37, 80.4%) or biliary (n = 9, 19.6%) carcinoma received 3 mg/m2 raltitrexed intravenously once every 3 weeks. For the quality of life assessments, EORTC QLQ-C30 was used, and the evaluation of the clinical benefit was performed according to the 4 criteria of the clinical benefit response. All patients were assessed for safety, and 41 patients were evaluable for objective response.


RESULTS
Patients (63% male/37% female) had a mean age of 61.2 years, 71.7% had a PS of 0-1, 78.3% had metastatic disease, and 63% had at least 2 tumoral sites. A total of 176 cycles were administered with a mean of 4 cycles per patient (range 1-12). Three out of 43 patients evaluable for EORTC QLQ-C30 (7.0%; CI(95%) 1.4-19.0%) had a quality of life improvement. Thirty-two patients fulfilled the 4 criteria required to evaluate the clinical benefit response; 5 were responders (15.6%; CI(95%) 5.3-32.8%); 1 patient was a good responder based on both the EORTC questionnaire and the clinical benefit response. Forty-one patients were assessable for response, 3 responded to treatment (response rate: 6.5 %; CI(95%) 1.3-17.9%). Median survival was 4.6 months (CI(95%) 2.9-8.2 months), the 1-year survival rate was 21.8%. The most common grade 3-4 toxicities were neutropenia (8%), leukopenia (8%), thrombopenia (6%), anemia (6%), liver enzyme elevations (11%), asthenia (9%), vomiting (9%), abdominal pain (7%), and phlebitis (6%). One treatment-related death occurred (neutropenic sepsis).


CONCLUSIONS
Raltitrexed appeared to be generally well tolerated and showed a clinical benefit response and/or quality of life improvement in a limited number of patients.
François
Eric
E
Centre Antoine-Lacassagne, Nice, France. eric.francois@cal.nice.fnclcc.fr
Hebbar
M
M
Bennouna
J
J
Mayeur
D
D
Perrier
H
H
Dorval
E
E
Martin
C
C
Bourgeois
H
H
Barthélemy
P
P
Douillard
J Y
JY
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D013876:Thiophenes / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; D013940:Thymidylate Synthase; C068874:raltitrexed