Ann. Pak. Inst. Med. Sci. 2010; 6(2): 85-90

Objective: The primary objective of the study was to compare the efficacy and safety of adjuvant chemotherapy (ACT) with neoadjuvant chemotherapy (NACT) in patients with ovarian epithelial cancer (OEC).
Place & Duration of Study: This Randomized Controlled Trial was conducted at Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore (Pakistan). Patients were enrolled and treated over one year from August 2008 to July.2009.
Patients & Methods: Total of 31 patients with advanced ovarian cancer who were selected by consecutive (non probability) sampling were divided into 2 groups to receive platinum-based chemotherapy in either adjuvant (n = 14) or neoadjuvant setting (n = 17). Efficacy was determined using radiological, pathological and biochemical (CA-125) response rates at the completion of treatment. Adverse effects of chemotherapy were noted to assess the safety of therapy.
Results: Patients in ACT arm showed superior radiological (92.9% vs. 54.4%, p = 0.039) and pathological (64.3% vs. 11.8%, p = 0.001) response rates as compared to patients in NACT arm. Higher number of patients in ACT arm were able to have optimal cytoreductive surgery than in NACT arm, but this could not reach statistical significance (85.7% vs. 76.4%; p = 0.664), probably due to small study population size. Biochemical response rates were better in NACT group (94.1% vs. 84.7%; p = 0.564). Both hematological and non-hematological adverse effects were higher in women treated with NACT.
Conclusion: Use of ACT is more efficacious and safe for patients with ovarian epithelial cancer as compared to NACT.
Key Words: Ovarian Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Adjuvant Chemotherapy; Neoadjuvant therapies

Introducation

Ovarian epithelial cancer (OEC) is the 5th leading cause of cancer-related deaths among women in America where it accounts for 3% of all women cancers. In 2008, over 21 thousand new cases of ovarian cancer were diagnosed in the United States and about 15 thousand women died of that disease. ¹ From the currently available limited information, it is estimated that ovarian cancer is the fourth most common cancer among females in Pakistan. ² Ovarian epithelial cancer (OEC) is a silent killer as most patients experience no symptoms while disease continues to progress.³ As a result, most patients actually present at an advanced stage, thus resulting into high mortality.⁴ The optimal cytoreductive surgery (OCRS) followed by adjuvant chemotherapy (ACT) is currently considered the standard treatment for advanced OEC in many centers.⁵
There is an inverse relationship between survival and amount of residual disease after surgical resection. Only OCRS, defined as less than 2 cm residual tumor after surgical debulking, has shown survival benefit in published trials.5 Upfront OCRS is often difficult to achieve in advanced ovarian cancers due to the large tumor bulk. Most of these patients will relapse and die of their disease, making role of upfront surgery questionable in this setting. ^{6, 7}
In order to achieve optimal cytoreduction in patients with advanced disease, the strategy of interval cytoreduction has been introduced. Interval cytoreduction involves repeating an attempt at debulking surgery after several cycles of chemotherapy, when optimal cytoreduction is not possible due to bulky disease. With the use of platinum-based chemotherapeutic regimens, response rates as high as 80% have been reported.8 After use of adjuvant chemotherapy in patient with residual disease, OCRS was possible in 50 to 90% patients.9 This concept has evolved into the development of neoadjvuant chemotherapy (NACT) where an initial attempt at surgical cytoreduction is abandoned in favor of chemotherapy. The idea is to reduce the tumor burden and improve the functional status of the patients, making optimal cytoreduction easier. ^6,8
Another study published the results of first series on NACT with encouraging results.¹⁰ It was followed by more than 20 small retrospective and prospective phase I and II studies resulting in dramatic clinical responses and despite concerns, progression-free survival and overall survivals were not compromised.6 European Organization for Research and Treatment of Cancer (EORTC) is conducting a phase III trial in which platinum-based chemotherapy is being compared in adjuvant and neoadjuvant settings. ¹¹ The results of this trial will help in better understanding of the management of advanced OEC.
The only documentation of use of NACT in an advanced OEC in our country was a case report describing a positive outcome.¹² However our study will be the first of its kind as a Randomized Control trial from Pakistan, comparing the results of ACT with NACT in advanced OEC.