The triple modality of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with cisplatin is a highly active treatment for locally advanced cervical carcinoma with acceptable toxicity.

The results of this non-randomized comparison suggest that induction chemotherapy followed by surgery or chemoradiation is at least as effective in terms of response and survival as standard cisplatin-based chemoradiation. A randomized study is needed to confirm these findings.

Induction chemotherapy followed by surgery, particularly with newer agents or combinations, remains to be explored in locally advanced cervical cancer. Gemcitabine cisplatin is a very active combination for this tumor, therefore we explored the activity of gemcitabine in combination with oxaliplatin. Ten untreated patients with histologic diagnosis of cervical carcinoma and staged as IB2 to IIIB were treated with 3 21-day courses of oxaliplatin 130 mg/m day 1 and gemcitabine 1,250 mg/m days 1 and 8 followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated at the end of chemotherapy. All patients were evaluable. The overall clinical response rate was 80%, being complete in 3 patients (30%) and partial in 5 (50%). Seven (70%) patients underwent surgery, and three (30%) had chemoradiation as definitive treatment. Hematologic toxicity was moderate, with leukopenia grades III-IV in 17 and 0%; granulocytopenia grades III-IV in 23 and 3%, respectively. Eight patients had grade I oropharyngeal toxicity. At a median follow-up of 11 months (range: 10-12), all patients are disease free. Gemcitabine oxaliplatin is a very active and well-tolerated combination for locally advanced cervical cancer.

Neoadjuvant chemotherapy followed by surgery is a promising approach in locally advanced cervical carcinoma. The aim of this study was to evaluate the feasibility, technical aspects, and clinical results of surgery after induction chemotherapy in this patient population. Forty-one untreated cervical carcinoma patients staged as IB2 to IIIB received three 21-day courses of cisplatin 100mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8 followed by surgery or concomitant chemoradiation. The response to chemotherapy, operability, surgical/pathological findings, disease-free period, and survival of the surgically treated patients were evaluated. All 41 patients were evaluated for toxicity and 40 were evaluated for response. The overall objective response rate was 95% (95% confidence interval 88%-100%), and was complete in three patients (7.5%) and partial in 35 (87.5%). Granulocytopenia grades 3/4 occurred in 13.8% and 3.4% of the courses, respectively, whereas nonhematological toxicity was mild. Twenty-three patients underwent type III radical hysterectomy. Mean duration of surgery was 3.8 h (range 2:30-5:20), median estimated blood loss was 670 ml and median hospital stay was 5.2 days. Intraoperative complications occurred in one case (venous injury). In all but one case the resection margins were negative. Four patients (17%) had positive nodes (one node each); six (26%) had complete pathologic response, three (13%) had microscopic; and 14 (60%) macroscopic residual disease. At 24 months of maximum follow-up (median 20), the disease-free and overall survival rates were 59% and 91%, respectively. Induction chemotherapy with cisplatin/gemcitabine produced a high response rate and did not increase the difficulty of surgery. Operating time, blood loss, intraoperative complications, and hospital stay were all within the range observed for type III hysterectomy in early stage patients. We therefore conclude that type III radical hysterectomy is feasible in locally advanced cervical cancer patients who respond to chemotherapy.

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