A more recent study from Yale University demonstrated that patients treated with neoadjuvant chemotherapy consisting of carboplatin(Drug information on carboplatin) and paclitaxel did significantly better than those treated with carboplatin and cyclophosphamide(Drug information on cyclophosphamide). This finding was consistent with the GOG 111 study, which revealed that stage IIIC ovarian cancer patients with > 1 cm maximum diameter of residual disease or stage IV patients treated with cisplatin(Drug information on cisplatin) and paclitaxel(Drug information on paclitaxel) did statistically better than those treated with cisplatin and cyclophosphamide.
In the most recent Yale neoadjuvant chemotherapy study there was no difference in progression-free or overall survival for patients treated with carboplatin and paclitaxel given in a neoadjuvant chemotherapy regimen for six cycles followed by aggressive cytoreductive surgery or those treated initially with conventional cytoreductive surgery followed by the same combination chemotherapy for six cycles (Figure 1). Approximately 33% of patients in the Yale study who underwent conventional treatment were cytoreduced to no residual disease, whereas 80% of patients who received neoadjuvant chemotherapy first and then underwent surgery were cytoreduced to no residual disease.
The 18-month progression-free survival experienced for the patients receiving carboplatin and paclitaxel in both the neoadjuvant chemotherapy arm and the conventionally treated group was consistent with the intravenous chemotherapy experience reported in the GOG 172 clinical trial. All of the latter patients had stage III disease that was optimally surgically cytoreduced. The 83-month overall survival for the Yale neoadjuvant chemotherapy-treated patients compares favorably with the overall survival of 65.5 months for intraperitoneally treated patients in the GOG 172 clinical trial, especially since the GOG 172 protocol was confined to patients who were optimally cytoreduced to less than 1 cm of residual disease.[18,26] It also compares well to results from Eisenkop et al, who initially optimally cytoreduced 87.7% of stage IIIC patients and reported a 75.8-month median survival.
Stage IV Disease
Survival statistics for stage IV patients treated with neoadjuvant chemotherapy in the Yale series were statistically better for progression-free and overall survival compared to conventionally treated stage IV patients in that series (Figure 2). This observation is not new. Vergote et al reported in 1998 that patients treated with neoadjuvant chemotherapy for stage IV disease did better than conventionally treated patients. The recent Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO) stage IV ovarian cancer study reported that patients who were treated in a conventional fashion and were optimally cytoreduced had a 23-month overall survival, whereas those who received neoadjuvant chemotherapy for stage IV disease and then were optimally cytoreduced had a 46-month median duration of survival.
In my experience, neoadjuvant chemotherapy must be followed by surgery in order to achieve these excellent results. That surgery should be done by surgeons trained in gynecologic oncology who are willing to make a maximum surgical effort in order to achieve these results.
Stage IV patients initially presenting with malignant pleural effusions have a significantly poorer survival even when optimal cytoreductive surgery is performed in the abdomen and pelvis.[2,30] In an effort to determine the presence of intrathoracic disease and possibly to cytoreduce their disease, video-assisted thoracic surgery (VATS) has been evaluated in 21 patients with stage IV ovarian cancer based on the presence of a right-sided malignant pleural effusion. Of these 21 patients, 12 underwent cytoreductive surgery, 3 of whom had intrathoracic cytoreduction performed. Among these 12 patients, 11 had optimal cytoreduction to ≤ 1 cm in the pleural and peritoneal cavities following VATS.
The remaining 9 patients, 8 of whom initially had > 1 cm intrathoracic disease documented by VATS, received neoadjuvant chemotherapy followed by interval surgical cytoreduction. Six of the nine were surgically cytoreduced to no macroscopic residual disease. The remaining three patients were optimally cytoreduced to ≤ 1 cm following neoadjuvant chemotherapy. Survival data were not reported in this publication.
Impact of Histology
Patients who received neoadjuvant chemotherapy overwhelmingly had histologically poorly differentiated cancers.[25,26] However, a recent report suggested that neoadjuvant chemotherapy may not be effective in the treatment of low-grade serous cancers. Schmeler et al from M.D. Anderson Cancer Center reported on 25 patients with low-grade serous cancers of the ovary (n = 22) or peritoneum (n = 3) treated in a neoadjuvant fashion with platinum-based chemotherapy. Of these 25 patients, 11 (44%) underwent exploratory laparotomies first to determine surgical cytoreducibility. Only 1 patient had a complete clinical response to the chemotherapy, 21 had stable disease radiologically, and 2 progressed radiologically.
Similar discouraging findings were reported from this institution when patients with low-grade serous cancers were treated conventionally. Results included a 5% negative second-look surgery rate and a median progression-free survival of 19 months.
Advantages of Neoadjuvant Chemotherapy Over Conventional Therapy
Subjectively, patients who received neoadjuvant chemotherapy prior to surgery appear to be in better physical condition and emotionally better prepared to undergo the surgery. In part this is because successful neoadjuvant chemotherapy will eliminate pleural effusions and ascites, allowing patients to eat better and to return more rapidly to their normal state of health than when they undergo initial radical cancer surgery.
In the Yale experience, the operative time was significantly decreased (to 211 minutes) when neoadjuvant chemotherapy was administered followed by surgery than when surgery is done prior to chemotherapy (276 minutes). In addition, blood loss was significantly less with the neoadjuvant approach (546 vs 1,033 mL). Surgical intensive care unit stays were shorter (2 vs 1.6 days), and total hospitalization stays were significantly shorter (5.7 vs 8.5 days).