On the basis of epidemiologic and experimental evidence of an anticancer activity of
vitamin A, a randomized clinical trial was activated in Milan with the aim of evaluating if
retinol palmitate administration (per os, 300,000 I.U. daily) after complete resection of stage Ia
non small-cell lung cancer could reduce the occurrence of
cancer relapses (within 3 years) and/or the occurrence of new primary
tumors (beyond 3 years). By September 1987, 181 patients had entered the trial: 87 in the treatment arm and 94 in the control arm. After a median follow-up of 14 months, the interim analysis was focused on the evaluation of toxicity, compliance, and early recurrences. Although the large majority of patients were affected by skin and mucous membrane desquamation and dryness during treatment, these symptoms were generally mild and well tolerated, and never induced the patient to stop the treatment. Other side effects like
headache,
hair loss,
itching, or
dyspepsia were detected at a much lower frequency. Only in 3 patients the treatment was interrupted, because of signs or symptoms potentially related to
vitamin A administration. At the time of the analysis, a total of 42 (23%) patients had relapsed; 16 (18%) in the treated arm, and 26 (28%) in the control arm. The largest difference between treated patients and controls was observed for bone
metastases (2 vs. 7) and
brain metastases (3 vs. 6), and for squamous histology (6 vs. 11). Only 2 cases of new primary
cancer were detected, both in the control arm. These results are promising both in terms of tolerance and efficacy of treatment, but given the short median follow-up they must be very cautiously interpreted. A longer follow-up is necessary to establish whether a significant proportion of early recurrences could be prevented, or only delayed, by
vitamin A administration.