Chemotherapy for advanced, recurrent, and metastatic cervical cancer.
ABSTRACT When cervical cancer is beyond curative treatment with surgery or radiation therapy, the prognosis is poor and palliation is the primary objective. Early prospective studies identified cisplatin as an active drug for advanced, metastatic, or recurrent cervical cancer, and results with other platinum analogs seemed inferior to cisplatin. Several phase III trials have established the combination of cisplatin plus paclitaxel as standard therapy for comparison. Using pooled data from 3 Gynecologic Oncology Group (GOG) phase III studies, a predictive model was developed to better identify patients who are unlikely to respond to cisplatin-containing chemotherapy. The GOG is currently developing a phase III trial to investigate the impact of bevacizumab and a regimen containing topotecan instead of cisplatin in combination with paclitaxel chemotherapy and also to externally validate the predictive model. This study has the potential to radically change standard care for cervical cancer chemotherapy. Furthermore, if the predictive model is upheld, then patients with high risk factors for treatment failure may be directed to chemotherapy regimens that do not include cisplatin or to investigational trials.
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ABSTRACT: BACKGROUND: Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma. METHODS: Patients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFNgamma-ELISPOT. RESULTS: No systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFNgamma, TNFalpha, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient's immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 +/- 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease. CONCLUSIONS: The HPV16-SLP vaccine was well tolerated and induced a broad IFNgamma-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor prevented progressive disease. We, therefore, plan to use this vaccine in combination with chemotherapy and immunomodulation.Journal of Translational Medicine 04/2013; 11(1):88. · 3.46 Impact Factor
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ABSTRACT: To define the recommended dose of the association of weekly irinotecan (Iri) and cisplatin (CP) with pelvic radiotherapy in Locally Advanced Cervical Cancer. Stage IB2-IV cervix cancer patients were treated with escalating doses of Iri starting from 30 mg/m(2) and a fixed dose of CP at 20 mg/m(2), both weekly concomitantly with a 45-Gy pelvic irradiation. Fifteen patients entered the study, 6 at level 1 (Iri 30 mg/m(2)), 3 at level 2 (Iri 40 mg/m(2)) and 6 at intermediate dose (Iri 35 mg/m(2)). Median age was 47 years (34-72), FIGO stage IB (n=1), IIB (n=7), III (n=6), IVA (n=1). The recommended dose was weekly Iri 35 mg/m(2) and CP 20 mg/m(2). Dose limiting toxicities (grades 3-4) were diarrhea, abdominal pain, febrile neutropenia and fatigue. In cervix cancer patients, radiosensitization with weekly cisplatin and irinotecan is feasible, and the recommended doses are cisplatin 20 mg/m(2)/week and irinotecan 35 mg/m(2)/week for future phase II studies.Gynecologic Oncology 03/2010; 117(2):276-80. · 3.93 Impact Factor
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ABSTRACT: The aim of this narrative review is to update the current knowledge on the treatment of recurrent cervical cancer based on a literature review. A web based search in Medline and CancerLit databases has been carried out on recurrent cervical cancer management and treatment. All relevant information has been collected and analyzed, prioritizing randomized clinical trials. Cervical cancer still represents a significant problem for public health with an annual incidence of about half a million new cases worldwide. Percentages of pelvic recurrences fluctuate from 10% to 74% depending on different risk factors. Accordingly to the literature, it is suggested that chemoradiation treatment (containing cisplatin and/or taxanes) could represent the treatment of choice for locoregional recurrences of cervical cancer after radical surgery. Pelvic exenteration is usually indicated for selected cases of central recurrence of cervical cancer after primary or adjuvant radiation and chemotherapy with bladder and/or rectum infiltration neither extended to the pelvic side walls nor showing any signs of extrapelvic spread of disease. Laterally extended endopelvic resection (LEER) for the treatment of those patients with a locally advanced disease or with a recurrence affecting the pelvic wall has been described. The treatment of recurrences of cervical carcinoma consists of surgery, and of radiation and chemotherapy, or the combination of different modalities taking into consideration the type of primary therapy, the site of recurrence, the disease-free interval, the patient symptoms, performance status, and the degree to which any given treatment might be beneficial.Surgical Oncology 01/2012; 21(2):e59-66. · 2.14 Impact Factor