13-cis-Retinoic acid in combination with gemcitabine in the treatment of locally advanced and metastatic pancreatic cancer--report of a pilot phase II study.
OBJECTIVE
Adenocarcinoma of the pancreas is a cancer with extremely poor prognosis and limited therapeutic options. Retinoids are derivatives of vitamin A involved in the control of many biological functions, including cell growth and differentiation and the induction of apoptosis. On the basis of pre-clinical evidence and some clinical data, we conducted a phase II study of 13-cis-retinoic acid (13-cis-RA) in combination with gemcitabine in patients with unresectable pancreatic carcinoma.


METHODS
Patients with histologically confirmed unresectable pancreatic carcinoma were treated with gemcitabine 1000 mg/m2 on days 8, 15, 22 plus 13-cis-RA 1 mg/kg on days 1-14 for six cycles. The end points included the objective response rate and median survival.


RESULTS
Thirty patients were recruited, 15 men and 15 women; 20 patients were evaluable. The median age was 65 years (range 44-79 years) and the median Karnofsky performance status was 80% (range 60-100%). The median follow-up was 21 months. One patient achieved a partial remission, seven patients had stable disease and 12 patients developed progressive disease. Toxicity was mainly haematological, with eight cases of grade 3 and four cases of grade 4 neutropenia, thrombocytopenia and anaemia. The median survival was 7.8 months (range 2.6-21.6 months).


CONCLUSIONS
The combination of gemcitabine and 13-cis-RA was well tolerated, but we did not see improvement in the response rate. Further studies with other retinoids may be beneficial to patients with unresectable pancreatic cancer.
Michael
A
A
Oncology Department, St George's Hospital, St James' Wing, Blackshow Road, London SW17 0QT, UK. amichael@sgul.ac.uk
Hill
M
M
Maraveyas
A
A
Dalgleish
A
A
Lofts
F
F
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010166:Palliative Care; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010865:Pilot Projects; D011379:Prognosis; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; D015474:Isotretinoin; D000093542:Gemcitabine