Gynecologic cancer updateRecent Achievements and Future Developments in Advanced and Recurrent Cervical Cancer: Trials of the Gynecologic Oncology Group
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Single-Agent Cisplatin Versus Platinum Doublets
During the preceding three decades, the GOG has been studying the efficacy and tolerability of many cytotoxic regimens for metastatic and recurrent cervical cancer.3 On behalf of the GOG, McGuire and colleagues had reported a 17% overall RR for single-agent paclitaxel in advanced squamous cell carcinoma of the cervix,15 and when combined with cisplatin as part of a single-arm phase II feasibility study, an impressive overall objective RR of 46% was demonstrated.6 While the superior RR was
Prognostic Markers for Predictive Modeling
Moore and colleagues recently performed a pooled analysis of three published phase III GOG studies of cisplatin versus cisplatin-containing combinations (protocols 110, 169, and 179)7, 10, 13 to identify factors that would permit the development of a model predictive of non-response to chemotherapy.16 The investigators evaluated age, race, performance status, stage, histology, grade, disease site, prior chemotherapy with primary radiation, time to recurrence, and single-agent versus combination
Four-Arm Randomized Study of Cisplatin Doublets
The recent completion of GOG 204 represents the largest randomized trial in cervical cancer performed in the world. The trial, conducted by the GOG between 2003 and 2007, recruited women with stage IVB, recurrent or persistent cancer not amenable to cure to one of four chemotherapy regimens. Specifically, women were randomized equally among four cisplatin doublets: paclitaxel 135 mg/m2 over 24 hours plus cisplatin 50 mg/m2 day 2 every 3 weeks (PC, reference arm); vinorelbine 30 mg/m2 days 1 and
Evaluation of Non–Platinum Doublets
With the adoption of platinum-based chemo-irradiation as the standard of care for locally advanced disease, it becomes important that non–platinum doublet therapies undergo rigorous investigation in the recurrent/metastatic setting. While several potential doublets can be considered, data from prospective studies in women with advanced cervical cancer treated with prior platinum are limited to a few small phase II studies.
At the 2007 Annual Meeting of the American Society of Clinical Oncology,
Angiogenesis
The inability of conventional cytotoxic agents to enhance long-term survival is likely multifactorial. First and foremost, cervical cancer (even untreated cervical cancer) is not a particularly chemotherapy-sensitive disease with clinical CRs to multi-agent chemotherapy being rare. In women suffering from metastatic cervical cancer who typically have been previously irradiated (and therefore harbor radioresistant and chemoresistant tumor cell populations) dramatic tumor cytoreduction,
Clinical Trials with Bevacizumab
In patients receiving an irinotecan plus fluorouracil/leucovorin (IFL) regimen for first-line treatment of metastatic colorectal cancer, the addition of bevacizumab (5 mg/kg dosed every other week) significantly increased overall survival by 4.7 months relative to IFL plus placebo.32 In the second-line treatment of advanced colorectal cancer, patients who received bevacizumab (10 mg/kg biweekly) in combination with a fluorouracil/leucovorin plus oxaliplatin (FOLFOX4) regimen had an overall
Single-Agent Bevacizumab for Metastatic Cervical Cancer
Given the activity of bevacizumab in a variety of solid tumors, a phase II evaluation of bevacizumab at 15 mg/kg delivered on an every-21-day schedule was undertaken within the GOG (protocol 227C).4 Among the 46 eligible and evaluable patients, 38 (82.6%) had received prior pelvic radiation as well as either one (n = 34, 73.9%) or two (n = 12, 26.1%) cytotoxic regimens for recurrent disease. Notable grade 3/4 adverse effects at least possibly related to bevacizumab included hypertension (n =
Bevacizumab Plus Chemotherapy in Pre-Irradiated Patients
In 2006, Wright and collaborators reported the clinical course of six heavily pretreated cervical cancer patients who received combination chemotherapy (5-fluorouracil or capecitabine) plus bevacizumab (5-15 mg/kg) for recurrent disease.41 Five patients originally had been treated with primary chemo-irradiation, and at recurrence all had multi-site metastatic disease. Clinical benefit was noted in four of the six subjects, including one CR one PR, with the remaining two patients demonstating
Therapeutic HPV Vaccine Technology
In June 2006, the FDA approved the quadrivalent HPV 6/11/16/18 virus-like particle (VLP) for females aged 9 years to 26 years as a prophylactic vaccine for the prevention of human papilloma virus (HPV) -induced genital warts and cervical neoplasia. Even if widespread prophylactic vaccination is adopted at the national or even global level, it will take at least one generation before dramatic decreases in the incidence of cervical cancer will be observed. Even so, because the HPV subtypes
Beyond Platinum for Recurrent and Metasatic Cervical Cancer
Because prognosis is so poor for women with metastatic and/or recurrent cervical cancer and therapy is typically palliative in nature, there is a need to evaluate novel regimens for this disease. This population also warrants study of prognostic markers or more importantly predictive markers that may provide rationale guidance to the selection of therapies. Because none of the experimental arms in GOG protocol 204 outperformed the reference arm of cisplatin plus paclitaxel7 it is reasonable for
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Invasive cervical cancer
2023, DiSaia and Creasman Clinical Gynecologic OncologyLong-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial
2021, Gynecologic OncologyCitation Excerpt :In a systematic review and meta-analysis of 2445 patients (CRT: n = 1217; RT: n = 1228) with locally advanced cervical cancer (stages IIB–IVA, FIGO 2009), CRT as shown to improve complete response (+10.2%, p = 0.027), long-term loco-regional control (+8.4%, p < 0.001) and OD (+7.5%, p < 0.001) compared with RT alone. Therefore, the body of evidence confirming that CRT improves therapeutic outcomes in patients with advanced cervical is growing rapidly [14–19]. The univariate analysis in the present study showed that KPS ≥90%, unilateral parametrial invasion, absence of (or proximal) vaginal invasion, and baseline hemoglobin ≥10 mg/dL, but not treatment arm, were associated with improved DFS and OS.
Invasive cervical cancer
2018, Clinical Gynecologic OncologyThiazolidinediones abrogate cervical cancer growth
2017, Experimental Cell ResearchNovel Therapies for Advanced Cervical Cancer
2017, Translational Advances in Gynecologic Cancers