Open-label trial on efficacy and security of treatment with gemcitabine and oral modulation with tegafur and levofolinic acid (GEMTG) in patients with advanced pancreatic cancer.
OBJECTIVE
Advanced pancreatic cancer has a bad prognosis, with a median overall survival (OS) no longer than 4-6 months. Since the end of last century, monotherapy with gemcitabine has remained the elective therapy, but new schedules are needed in order to improve these results. We aim to evaluate the efficacy of tegafur and levofolinic acid (LV) associated with gemcitabine, as well as its toxicity, progression-free survival and OS in advanced pancreatic cancer.


METHODS
An open-label, multicentric, prospective, non-controlled trial was carried out on patients with advanced or disseminated pancreatic cancer. Gemcitabine 1250 mg/m² was administered on the 1st and 8th days of the cycle, tegafur 750 mg/m²/day for 21 consecutive days and LV 25 mg/day continuously, every 28 days, with a maximum of six cycles. The primary variable was tumour overall response rate (ORR). Secondarily, time to progression (TTP), OS and scheme toxicity were determined.


RESULTS
Forty patients were recruited; the male/female ratio was 30:10, with a mean age of 61 years. Forty percent had a Karnofsky index of 90% or 100%. Only 11 patients (27%) completed the six cycles of treatment, but more than 50% received three or more cycles. Dose intensity was 89.56% for gemcitabine and 87.36% for tegafur. Efficacy ORR was 22.5% (CI 95%, 6-37%). TTP was 3.87 months (CI 95%, 2.1-5.6), time to treatment failure was 2.97 months (CI 95%, 2.43-4.67) and OS 6.3 months (CI 95%, 4-7). The chemotherapeutic combination was well accepted; most haematologic and non-haematologic toxicities were grade 1 or 2. The most prevalent grade 3/4 toxicities were asthenia (30%), liver biochemistry disorders (25%), diarrhoea (15%) and stomatitis (12%).


CONCLUSIONS
The administration of gemcitabine, associated with oral tegafur and leucovorin, has activity against advanced pancreatic cancer, with an adequate toxicity profile.
Oncology Department, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain. cpericay@gmail.com
Carles
C
Pericay Pijaume
Pilar
P
Escudero Emperador
Román
R
Bastús Piulats
Juan Manuel
JM
Campos Cervera
Gaspar
G
Esquerdo Galiana
Manuel
M
Gallén Castillo
Jordi
J
Alfaro Gamero
Emma
E
Dotor Navarro
Aleydis
A
Pisa Gatell
Inmaculada
I
Guasch Jordán
Eugeni
E
Saigí Grau
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D005641:Tegafur; D002955:Leucovorin; D000093542:Gemcitabine
J Clin Oncol. 2007 Jun 20;25(18):2607-15
17577041
J Clin Oncol. 2002 Aug 1;20(15):3270-5
12149301
Ann Oncol. 1996 Aug;7(6):593-600
8879373
J Clin Oncol. 2009 Nov 20;27(33):5513-8
19858379
CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
15761078
J Clin Oncol. 1997 Jun;15(6):2403-13
9196156
J Clin Oncol. 2009 May 1;27(13):2231-7
19307500
Eur J Cancer. 2005 Oct;41(15):2241-9
16214045
Am J Clin Oncol. 1983 Apr;6(2):181-6
6402917
Oncology. 1986;43(4):212-5
3088506
J Clin Oncol. 2007 May 20;25(15):1960-6
17452677
J Clin Oncol. 2002 Jul 15;20(14):3130-6
12118027
Clin Transl Oncol. 2009 May;11(5):290-301
19451062
Cancer. 1998 Jul 15;83(2):254-8
9669807
Oncology. 1995 Mar-Apr;52(2):167-9
7854779
J Clin Oncol. 2007 Jun 1;25(16):2212-7
17538165
Br J Cancer. 2005 Jul 25;93(2):185-9
15986036
BMC Cancer. 2008 Mar 28;8:82
18373843
J Clin Oncol. 2005 May 20;23(15):3509-16
15908661
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
10655437