Neoadjuvant chemotherapy before surgery in cervical cancer

Eighteen phase II clinical trials have demonstrated the relative ease of administering intravenous neoadjuvant chemotherapy before radical surgery in patients with cervical cancer. Toxicity has been modest, with the exception of occasional severe bleomycin-induced pulmonary toxic effects. All regimens tested have been cisplatin based with no clearly superior combination. Overall objective response rates were 85% for patients with International Federation of Obstetrics and Gynecology stage IB or IIA disease, 88% for those with stage IIB disease, 74% for those with stage III disease, and 47% for those with stage IV disease. There was a corresponding decrease in clinical complete response rates with increasing stage from 28% for those with stage IB or IIA disease to 7% for those with stage IV disease. Operability was also stage dependent: 94% for patients with stage IB and IIA disease, 74% for patients with stage IIB disease, and 58% for patients with stage III or IV disease. All inoperable patients received primary radiation therapy. Fifty-five percent of operable patients received postoperative radiation therapy. Most phase II trials using historical controls demonstrated comparable survival. Only a few trials showed improved survival with the use of neoadjuvant chemotherapy before radical surgery. To date, there has been only one reported prospective trial of neoadjuvant chemotherapy before surgery. Patients with stage IB disease were randomly assigned to receive radical hysterectomy and pelvic lymphadenectomy with or without neoadjuvant chemotherapy. A survival advantage was present only in patients with a tumor volume of greater than 60 cm3. Randomized, prospective trials of neoadjuvant chemotherapy followed by radiation therapy have shown either no advantage or a statistically significant reduction in survival when neoadjuvant chemotherapy is administered before radiation therapy. In light of this finding and the operability of only 58% of the patients with stage III or IV disease, it would be prudent to limit neoadjuvant trials to patients with stage I or II disease with an initial tumor volume of greater than 60 cm3. Four such trials either are under way or are approved an awaiting activation.