Interferon alpha-2a(LG Life Sciences Ltd.)

Patients with metastasising carcinoma of the uterine cervix or recurrent disease, in whom local treatment as surgery or radiotherapy has failed, are still an unsolved problem. Platinum-based multi-agent chemotherapies achieve overall response rates up to 60%, but side effects are serious and so far no survival benefit has been proven. Recent publications report on a synergistic effect of combination therapy using 13-cis-retinoic acid and interferon alpha-2 a in the treatment of squamous cell carcinoma of the cervix. In a pilot study we include 6 patients with locally recurrent or metastasising squamous cell carcinomas, five of the uterine cervix, one of the vulva. The systemic therapy consisted of-orally administered 13-cis-retinoic acid (80 mg q. d.) and subcutaneously injected interferon alpha-2 a (6 x 10(6) I.E. q. d.). All patients were primarily treated by surgical and/or radiation therapy. In each case chemotherapy had been either already performed or rejected by the patient. Median duration of treatment was 52 days, median survival time 107 days. Out of 6 patients 3 experienced progression of disease uninfluenced by therapy. One patient with multiple subcutaneous lymph node metastases showed mixed response for a short period of 3 weeks before progression and eventual death. One patient had no change or disease for 13 months with subsequent progression and eventual death after 22 months. One patient could not be evaluated for an allergic reaction after only 15 days of treatment. Other side effects were "flu-like symptoms", skin irritations, conjunctivitis sicca and chileitis, all WHO 1-2. Overall toxicity must be rated low compared to standard chemotherapy, but is not negligible. In our study the positive reports in literature concerning the treatment of primary advanced cervical cancer and recurrent advanced carcinoma of the skin could not be reproduced. This might be due to the small number of cases, which is a common problem in immunotherapeutic studies. Moreover, very unfavourable patient selection criteria in our study compared to primarily untreated patients may also have contributed to different response rates. However, in our opinion the tested regimen cannot be considered sufficiently effective in patients suffering from pretreated, recurrent squamous cell carcinoma of the cervix or vulva.

Patients presenting with advanced or metastatic colorectal carcinoma were randomized to treatment with either 5-Fluoro-Uracil + leucovorin or 5-Fluoro-Uracil + interferon alpha-2-a. Longitudinal series of Carcino-embryonic-antigen were obtained and analyzed with a dynamic model in seven of 16 patients had CEA levels above 10 ng ml-1. Clinical evaluation based on X-ray, ultrasound and CT-scans showed a partial response to the given treatment in three of the seven patients. The dynamic model consistently estimated the maximal accumulated cell kill (approximately three logs) in the patients experiencing a clinical response. The remaining four patients with CEA levels above 10 ng ml-1 showed some reduction in CEA as a consequence of the treatment cycles, although no clinical response could be established. No response was seen among the remaining nine patients with CEA levels below 10 ng ml-1.