A Phase II Study of Paclitaxel, Carboplatin, and Radiation with or without Surgery for Esophageal Cancer
A recent article published in the Journal of Thoracic Oncology studied the efficacy of a combined regimen of Paclitaxel, Carboplatin, and radiation with or without surgery for the treatment of oesophageal cancer. The rationale for conducting the study was based on the highly toxic side effect profile associated with the current standard treatment of Cisplatin-based chemoradiotherapy (CRT). The observed results lead to the conclusion that this new combination regime was fairly well tolerated amongst study participants, and promised efficacy in treatment of oesophageal cancer.
Oesophageal cancer usually holds a poor prognosis for patients, with an estimated 13,770 deaths in the USA in 2006, and an expected 3-year survival of localised cases approximating 15-30%. It is believed that the incidence of lower oesophageal and gastroesophageal adenocarcinoma is rapidly on the rise, and this rate has been stated as being greater than any other malignancy inflicting North Americans. Estimates reveal the occurrence of 14,450 new cases in the USA in 2006, and of these, many may in fact be metastatic or unresectable. Based on previous findings, of those patients with resectable disease, only a minority of them are solely cured by surgery. The standard treatment for locally advanced oesophageal cancers involves the use of CRT, the practice of which arose as a result of a landmark study performed by the Radiation Therapy Oncology Group (RTOG). Cisplatin is often the chemotherapeutic agent employed in the treatment of such cancers, however, this has widely displayed toxicities in terms of its high emetogenicity and associations with renal dysfunction. Another obvious complication of Cisplatin use is its requirement for prolonged intravenous hydration, which may prove to be difficult at times. In efforts to improve such complications, the suitability of other platinums was explored and Carboplatin, in particular, was seen to provide a better therapeutic option in terms of limiting side effects. It has since been adopted into regular practice as the platinum agent of choice for ovarian and non-small cell lung cancers (NSCLC). Studies of its effects in oesophageal cancers display promising results when used in conjunction with Paclitaxel. The safety and efficacy of this combination has already been determined in previous studies of twice weekly Paclitaxel, weekly Carboplatin, and radiation therapy for the treatment of stage III NSCLC. Thus, this study analysed the role of this combination in oesophageal cancers. Patient selection was based on those presenting with stages II to IV of the disease, and participants were administered a 30mg/m2 twice weekly dose of IV Paclitaxel for a total of 10 doses and a weekly 1.5mg/ml/min dose of IV Carboplatin for 5 doses. Non-surgery patients were given an extra dose of each agent for equivalency. CRT was then initiated at a dose of 45Gy, with the exception of non-surgical patients, who received 50.4Gy. Four-six weeks post-CRT, an oesophagectomy was performed on those participants planned to undergo surgery. Those exempted from the surgery were delivered two cycles of consolidation chemotherapy, comprising 200mg/m2 of Paclitaxel and AUC 6 of Carboplatin; with a 3-week break in between. Results displayed a rapid improvement in patient symptoms 2 weeks post-therapy in 90% of cases, which provides definite justifications for its remarkable efficacy. From the toxicity perspective, also, the results appeared promising, as only 19% of patients experienced grade III/IV nausea and emesis, and all other side effects were even less prevalent, and comprised grade III/IV neutropenia and oesophagitis in 10% of patients. There was also a comparable increase in the 3-year survival rate to include >60% of patients. Further trials involving larger sample sizes are required to directly compare the safety and efficacy of this therapy to the current standard of Cisplatin based CRT. (Source: Wang H, Ryu J, Gandara D, et al. A Phase II Study of Paclitaxel, Carboplatin, and Radiation with or without Surgery for Esophageal Cancer. Journal of Thoracic Oncology 2007; 2(2); 153-7. : April 2007.)