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.
[show abstract] [hide abstract]
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. · 2.44 Impact Factor
Article: Phase I study of irinotecan and cisplatin in combination with pelvic radiotherapy in the treatment of locally advanced cervical cancer: A GINECO trial.[show abstract] [hide abstract]
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. · 3.89 Impact Factor
Article: Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin.[show abstract] [hide abstract]
ABSTRACT: One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic.BMC Cancer 01/2010; 10:207. · 3.01 Impact Factor