Capecitabine and oxaliplatin for advanced gastric and oesophageal (oesophago-gastric) cancer - 6th draft.pub

• Gastric and oesophageal cancer are the fifth and ninth most common cancers in the UK – audit data from English Cancer Registries show that in 2005 there were 4680 patients diagnosed with gastric cancer and 6375 diagnosed with oesophageal cancer. Most patients present with advanced, inoperable or metastatic disease – in 2005 only 20% of patients that presented with this disease underwent surgical resection. This review considers the management of the advanced form of both cancers (i.e. locally advanced or inoperable). The term oesophago-gastric cancer will be used throughout the review as an umbrella term for both cancers since both are treated similarly. • The most established first –line treatment regimen for the treatment of advanced oesophago-gastric cancer in the UK contains epirubicin, cisplatin and infused fluorouracil (ECF). ECF is reported to be better tolerated and to have a more favourable risk reduction and median survival than other regimens. • Fluorouracil in the ECF regimen can be substituted with capecitabine (ECX). The proposed benefits of this substitution include patient convenience and elimination of central line related complications. Likewise when cisplatin in the ECF regimen is substituted with oxaliplatin (EOF), the potential requirement for lengthy hydration is reduced thereby potentially reducing administration time by up to six hours. When both fluorouracil and cisplatin are substituted the regimen is known as EOX. • The REAL2 study, the pivotal Phase III study in oesophago-gastric cancer, found capecitabine (as in ECX or EOX) and oxaliplatin (as in EOX or EOF) to be as equally effective as fluorouracil (as in ECF or EOF) and cisplatin (as in ECX or ECF), respectively. An overall response rate of between 40-48% was achieved, progression free survival was between 6.2-7.0 months and overall survival was between 9.3-11.2 months for the four treatment groups. • Toxicity of capecitabine and fluorouracil were similar and oxaliplatin was associated with less grade 3 or 4 neutropenia, alopecia, renal toxicity and thromboembolism but with more grade 3 or 4 diarrhoea and neuropathy than cisplatin. • One Phase III study (conference abstract) in gastric cancer demonstrated that when capecitabine was substituted for fluorouracil in combination with cisplatin, the substitution was considered to be non-inferior in terms of overall survival (5.6 months for capecitabine and cisplatin versus 5.0 months for fluorouracil and cisplatin). • Another Phase III study showed a trend towards improved progression free survival and overall survival when substituting oxaliplatin for cisplatin in combination with fluorouracil. • In one Phase II study, four patients who were exposed to a higher dose of capecitabine (1000mg/m) had grade 5 treatment related toxicities resulting in death. • Based on the average patient (1.7m), the BNF-listed drug costs of one cycle of each regimen is: ECF, £352; ECX, £424; EOF, £923; EOX, £995. However with the discounts available to NHS Trusts it is likely that the ECX may actually cost about £320 per cycle and EOX may cost approximately £400 per cycle. • The use of capecitabine instead of fluorouracil (i.e. use of ECX or EOX instead of ECF) removes the need to insert a central line, incur pump costs and also reduces the need for hospital/ day-care attendance from 3 to 1 per cycle. According to data from Roche, over 6 cycles this reduces the associated administration cost from £4551 to £1660. • The use of oxaliplatin instead of cisplatin reduces the need for pre-hydration – this may have logistical benefits for patients that have to travel long distances to treatment centres, have a beneficial impact on quality of life and may reduce pressure on day-care treatment centres. However we were unable to identify any material which enabled us to quantify these benefits and it is only likely have a marginal effect on overall administration costs. • Assuming 15 patients per 100,000 patient population in England are eligible for treatment with one of these regimens and receive an average 4 cycles of treatment – then at typical NHS prices if EOX was chosen as the regimen of choice (over the current standard ECF), it would cost an additional £6,000 per 100,000 patient population with no significant change in associated administration costs. Produced for the London New Drugs Group