13-cis-retinoic acid plus interferon alpha-2a: highly active systemic therapy for squamous cell carcinoma of the cervix.

BACKGROUND: Chemotherapeutic study of cervical squamous cell carcinoma has shown some positive results. Complete plus partial (overall) response rates of 15%-35% (complete response rate, less than 5%) were achieved with the use of a small number of cytotoxic single agents in patients with advanced disease. In addition, overall response rates of 60%-70% (complete response rates, 10%-20%) were achieved with cisplatin-based, multiagent regimens in patients with primary, locally advanced disease. However, the lack of clear evidence that existing chemotherapy can achieve a survival benefit, coupled with the worldwide annual deaths of hundreds of thousands of women from cervical cancer, indicates the urgent need for effective systemic therapy for this disease. PURPOSE: In view of the preclinical and clinical evidence that supports testing of the novel combination of 13-cis-retinoic acid (13-cRA) plus interferon-alpha (IFN-alpha) in cervical squamous cell carcinoma, we conducted a phase II study of this regimen in locally advanced disease. METHODS: Twenty-six patients with untreated, locally advanced squamous cell carcinoma of the cervix were treated daily for at least 2 months with oral 13-cRA (1 mg/kg) and subcutaneous recombinant human IFN alpha-2a (6 million units). In 21 patients (81%), the disease was stage II or higher. RESULTS: Thirteen patients (50%) experienced major responses (tumor regression greater than or equal to 50%) in association with resolution of symptoms; one achieved complete response, and 12 experienced partial response. Seven with partial response are improving further, four are being maintained in partial response, and one responder has relapsed during therapy. The response rate is 58% (11 of 19) in patients with stage IIB or higher disease and 66% (10 of 15) in patients with bulky disease (at least one dimension greater than or equal to 10 cm). Of the 13 non-responders, nine have stable disease and four have had disease progression during therapy. Toxicity was minimal. CONCLUSION: These preliminary results indicate that systemic 13-cRA plus IFN alpha-2a is a highly active, well-tolerated therapy for locally advanced cervical cancer.

[Treatment of 32 cervico-uterine cancer patients with 13-cis-retinoic acid and interferon alpha]. / Tratamiento de 32 pacientes con carcinoma cérvico-uterino con ácido 13-cis retinoico e interferón alfa.

BACKGROUND: The use of chemotherapy for cervical squamous cell carcinoma has shown some positive results. Total percentage of complete plus partial responses are near 30% with the use of single cytotoxic agents. Higher percentages are achievable with combined chemotherapy including platinum but the lack of evidence that current chemotherapy can increase survival, coupled with a devastating worldwide mortality, indicates the urgent need for more effective therapies. OBJECTIVE: To further assess the role of 13-cis-Retinoic acid (13-cRA) plus interferon alfa (IFN-alfa) in a prospective phase II trial in advanced cervical cancer. METHODS: Thirty two women with untreated cervical carcinoma, with median age of 42 years (24 to 60 years) and median Zubrod performance of 1 (range 0-2) were treated for at least two months with oral 13-cRA (1 mg/kg/day) and IFN-alfa 2a (subcutaneously, 6 million units daily). RESULTS: Sixteen patients (50%) had major responses, including four complete clinical responses. Major response rate in regard to disease stage were 100% in the four patients with stage IVA, 36% (4/11) in stage IIIB, 50% (4/8) in stage IIB, 50% (1/2) in stage IIA, and 43% (3/7) in stage IB. Remission of the cancer in 15 patients was reached after only two months of treatment and in one patient within one month. Dose escalations after two months of therapy in nonresponding patients had no effect. Toxicity to treatment was manageable. Twenty one patients had poorly differentiated tumors. CONCLUSIONS: These preliminary results indicate that systemic 13-cRA plus IFN-alfa 2a is a highly active, well tolerated therapy for locally advanced squamous cell carcinoma of the cervix, with potential to be used in the primary, adjuvant and salvage therapy of cervical cancer. This therapy warrants further study.

[Feasibility study: concurrent 13-cis-retinoic acid, alfa-2a interferon and radiotherapy in the treatment of 23 patients with advanced cervix uteri epidermoid carcinoma]. / Estudio de factibilidad: ácido 13-cisretinoico, interferón alpha-2a y radioterapia concurrentes en el tratamiento de 23 pacientes con carcinoma epidermoide cervicouterino avanzado.

The important therapeutic activity of 13-cRA and IFN-alpha-2a in carcinoma of squamous cells, cervical, without previous treatment, is confirmed. An unexpected result was the early toxicity of the biologic agents on the colon mucosa when they are combined with radiotherapy.

Adverse events following immunization with vaccines containing adjuvants.

A traditional infectious disease vaccine is a preparation of live attenuated, inactivated or killed pathogen that stimulates immunity. Vaccine immunologic adjuvants are compounds incorporated into vaccines to enhance immunogenicity. Adjuvants have recently been implicated in the new syndrome named ASIA autoimmune/inflammatory syndrome induced by adjuvants. The objective describes the frequencies of post-vaccination clinical syndrome induced by adjuvants. We performed a cross-sectional study; adverse event following immunization was defined as any untoward medical occurrence that follows immunization 54 days prior to the event. Data on vaccinations and other risk factors were obtained from daily epidemiologic surveillance. Descriptive statistics were done using means and standard deviation, and odds ratio adjusted for potential confounding variables was calculated with SPSS 17 software. Forty-three out of 120 patients with moderate or severe manifestations following immunization were hospitalized from 2008 to 2011. All patients fulfilled at least 2 major and 1 minor criteria suggested by Shoenfeld and Agmon-Levin for ASIA diagnosis. The most frequent clinical findings were pyrexia 68%, arthralgias 47%, cutaneous disorders 33%, muscle weakness 16% and myalgias 14%. Three patients had diagnosis of Guillain-Barre syndrome, one patient had Adult-Still's disease 3 days after vaccination. A total of 76% of the events occurred in the first 3 days post-vaccination. Two patients with previous autoimmune disease showed severe adverse reactions with the reactivation of their illness. Minor local reactions were present in 49% of patients. Vaccines containing adjuvants may be associated with an increased risk of autoimmune/inflammatory adverse events following immunization.