Dose-Dense Neoadjuvant Chemotherapy plus Radical Surgery in Locally Advanced Cervical Cancer: A Phase II Study

Abstract

Objective: To assess the efficacy and toxicity profile of dose-dense cisplatin-based neoadjuvant chemotherapy (NACT) followed by radical surgery in patients affected by locally advanced cervical cancer. Methods: Patients affected by carcinoma of the uterine cervix FIGO (International Federation of Obstetrics and Gynecology) stage IB2-IIIB were enrolled into the study. The treatment schedule consisted of 5 cycles of intravenous paclitaxel 60 mg/m² plus cisplatin 60 mg/m² every 10 days; patients were then submitted to radical hysterectomy and pelvic lymphadenectomy. Results: From January 2011 to March 2013, 22 patients were enrolled. Median age was 47 (26-83) years. FIGO stages included 1 IIA, 15 IIB, 1 IIIA, and 5 IIIB. Ninety-one percent of patients completed all the 5 planned cycles of NACT. Three patients experienced allergic reactions to paclitaxel. Grade 3-4 hematological toxicity was observed in 18% of cases. In 3 cases, grade 3-4 extra-hematological adverse and life-threatening events were reported (1 ototoxicity, 1 transient ischemic attack, and 1 myocardial infarction). No treatment-related death occurred. The operability rate was 86.4%. The overall response rate was 52.6%: 5 patients (26.3%) experienced clinical complete response, and 5 (26.3%) showed a clinical partial response. Stable disease was observed in 47.4% of patients, with no progressive disease recorded. Pathological response was observed in 57.9% of cases. Six out of 19 (31.6%) patients were submitted to adjuvant treatment. Conclusion: Dose-dense cisplatin-based NACT showed a response rate in approximately half of patients. However, in consideration of the reported extra-hematological toxicity, further studies on and new strategies with dose-dense platinum-based NACT are required to improve outcome in cervical cancer patients.

STAT3/IRF1 Pathway Activation Sensitizes Cervical Cancer Cells to Chemotherapeutic Drugs

“…Responses to neoadjuvant radio/chemotherapy vary greatly in patients (2,3). Intrinsic and acquired resistance of the neoplastic cells as well as substantial side effects from standard treatment including platinum-based chemotherapy limit the options for escalation (4).…”

Radical Surgery in Advanced Cervical Cancer Patients Receiving Bevacizumab-Containing Chemotherapy: A “Real Life Experience”

“…In the whole series, only 3 (20.0%) women had 3 grade 3 late events 25 especially after neoadjuvant treatment. 12 In this context, our results appear quite interesting, considering the common concerns about the potentially increasing technical difficulties, resulting from anti-VEGF target therapy (ie, inflammation, tissue, and vascular fibrosis), and possibly related to a higher risk of morbidity. Nonetheless, our results in terms of median estimated blood loss (250 mL; range, 50Y1500 mL) and median hospital stay (5 days; range, 2Y21 days) were also comparable to those previously reported with an open approach, regardless of the type of preoperatively administered treatment.…”

“…Indeed, promising data on survival are available from small retrospective series on stage III CC. 11,12 However, although clear data on safety of radical surgery after standard chemotherapy exist, 11,13 it does not exist on patients receiving bevacizumab-containing regimens. In fact, the addition of VEGF-targeting therapy could potentially increase the risk of surgical complications.…”

A note from history: Landmarks in history of cancer, part 7

“…220 Primary chemotherapy, or so-called neoadjuvant chemotherapy, a term coined at the US National Cancer Institute in 1982, gained fast popularity because of its potential for decreasing the size of the primary cancer and making it more amenable to surgical resection. 382 Successful application of neoadjuvant chemotherapy was demonstrated in bone and soft tissue arcomas, 273,345,347 uterine cervical carcinomas, 383 and breast carcinomas. 384 Later, it was demonstrated that preoperative chemotherapy decreased both the size of breast carcinomas and the incidence of positive axillary lymph nodes.…”