Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL), the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV) has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2) phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies.</p> <p>Methods</p> <p>Thirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 – 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated.</p> <p>Results</p> <p>No maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression. HPV DNA was negative in 48% of the previously positive patients. Long term follow-up did not reveal recurrences or adverse events.</p> <p>Conclusion</p> <p>CIGB 300 was safe and well tolerated. This is the first clinical trial where a drug has been used to target the CK2 phosphoaceptor domain providing an early proof-of-principle of a possible clinical benefit.</p

Ensaio clínico comparando três modalidades de crioterapia em mulheres não grávidas Ensayo clínico comparando tres tipos de crioterapia en mujeres no embarazadas Clinical trial comparing three types of cryotherapy in non-pregnant women

O estudo teve como objetivo comparar três modalidades de crioterapia em mulheres saudáveis e não grávidas. Trata-se de um ensaio clínico randomizado, não controlado, com 32 alunas do curso de graduação de uma faculdade de enfermagem particular da cidade de São Paulo, divididas em três grupos (gelo água, gelo mole, gelo gel). Foram verificadas as temperaturas (axilar, coxa e das três bolsas de gelo) entre zero e vinte minutos. As temperaturas das bolsas foram: gelo mole de 9°C negativos a 2°C, gelo água de 0°C a 8°C e gelo gel de 11°C negativos a 2°C. Houve diferença significativa entre as médias das temperaturas da coxa com 10 minutos (p=0,007), 15 minutos (p=0,003) e 20 minutos (p=0,005). O gel foi mais eficiente no resfriamento comparado aos outros dois métodos. As três modalidades de crioterapia atingem a temperatura recomendada para analgesia e podem ser aplicadas em puérperas com dor perineal após o parto normal.<br>El estudio tuvo como objetivo comparar tres modalidades de crioterapia en mujeres saludables y no grávidas. Se trató de un ensayo clínico randomizado no controlado con 32 alumnas del curso de graduación de una facultad de enfermería particular de la ciudad de São Paulo (Brasil). Las alumnas fueron divididas en tres grupos (agua helada, hielo blando, gel helado). Fueron verificadas las temperaturas (axilar, del muslo y de las tres bolsas de hielo) entre cero y veinte minutos. Las temperaturas de las bolsas fueron: hielo blando, de -9°C a 2°C; agua helada, de 0°C a 8°C; gel helado, de -11°C a 2°C. Hubo diferencia significativa entre las medias de las temperaturas del muslo tomadas a los 10 minutos (p=0,007), 15 minutos (p=0,003) y 20 minutos (p=0,005). El gel fue más eficiente en el enfriamiento comparado con los otros dos métodos. Las tres modalidades de crioterapia alcanzan la temperatura recomendada para la analgesia y pueden ser aplicadas en mujeres con dolor perineal posparto.<br>The objective of the present study was to compare three methods of cryotherapy in healthy non-pregnant women. This is a randomized controlled clinical trial that was conducted by 32 undergraduates of a private nursing college in the city of Sao Paulo, divided into three groups (iced water, soft ice, ice gel). The temperatures were verified (axillary, thigh, of the three ice packs) between zero and twenty minutes. The temperatures of the packs were the following: soft ice, from negative 9°C to 2°C; iced water, from 0°C to 8°C; and ice gel from negative 11°C to 2°C. There was a significant difference between the average thigh temperature values at 10 minutes (p=0.007), 15 minutes (p=0.003) and 20 minutes (p=0.005). The gel was the most efficient cooling method. The three cryotherapy methods achieved the recommended temperature for analgesia and may be tested in women with perineal pain after childbirth