Gem + CDDP + RT with adjuvant CDDP + Gem vs standard CTRT for cervical cancer

In the JCO:

I posted previously about this trial from Argentina when presented at ASCO 2 years ago, now the manuscript is published in the JCO. Essentially this trial asks two questions, the utility of concurrent gem with CDDP, and the utility of adjuvant chemotherapy. The overall effect is compelling in this manuscript, improved local control, DFS and OS, compared to standard CTRT with brachy, albeit at the cost of increased toxicity. I don't feel that a change in standard practice will occur in the US yet due to these results, as most US practitioners would like a confirmatory trial, preferably examining the gem question and the adjuvant chemo question separately. That said, for certain high risk patients, some of the Gynecologic Oncologists I work with have been giving adjuvant chemotherapy (CDDP based) due in part to these results.

Link and Abstract.

Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix [Gynecologic Cancer]: "Purpose

To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.

Patients and Methods

Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m² and gemcitabine 125 mg/m² weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m² on day 1, plus gemcitabine, 1,000 mg/m² on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A).

Results

Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A.

Conclusion

Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

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