Severe thrombocytopoenia (13%) and anaemia (2%) occurred much less frequently. The present results, in keeping with the key toxicities, are reported for first-line docetaxel/carboplatin in patients with advanced ovarian carcinoma (Vasey et al, 2004), that is 94, 9 and 11% grade 3/4 neutropaenia, thrombocytopoenia Vandetanib hypothyroidism and anaemia, respectively. The other most common treatment-related grade 3/4 AEs in the current study were diarrhoea, rash, febrile neutropaenia/infection (subsequent to severe chemotherapy-induced neutropaenia), fatigue and dehydration. Diarrhoea is common with docetaxel/carboplatin (Vasey et al, 2004) and with erlotinib (Shepherd et al, 2005). Similarly, fatigue is common to both chemotherapy and erlotinib (Vasey et al, 2004; Shepherd et al, 2005).

The rash observed in the present trial resulted from the erlotinib therapy, and has been reported in trials with erlotinib alone or in combination with chemotherapy in various tumour types (Gordon et al, 2005; Moore et al, 2005; Shepherd et al, 2005). Moreover, evidence indicates that the presence and severity of rash is correlated with survival in lung cancer (Perez-Soler et al, 2004), pancreatic cancer (Moore et al, 2005) and ovarian cancer (Gordon et al, 2005). As expected, AEs were more frequent with increasing doses of erlotinib in this trial. However, there was no evidence of cumulative toxicity as most patients completed the full six cycles of planned treatment. Various clinical trials have also demonstrated that combining erlotinib with chemotherapy is feasible in a wide variety of tumours.

In previously reported phase I/Ib trials, the MTD of erlotinib with cytotoxic agents ranged from 100mgday?1 (with capecitabine/docetaxel: Trigo et al, 2003; with Cilengitide capecitabine/oxaliplatin: van Cutsem et al, 2003; with docetaxel: Mita et al, 2002) to 150mgday?1 (with oxaliplatin/5-FU: Jones et al, 2003). The MTD of erlotinib of 75mgday?1 in the present trial is lower than in trials with other combinations. This finding may be due to the additive toxicities with docetaxel/carboplatin. Indeed, dose escalation of erlotinib to 150mgday?1 after chemotherapy suggests that erlotinib is better tolerated as a single agent in this patient setting. Although preclinical and early clinical trials demonstrated promising antitumour activity of erlotinib in combination with chemotherapy, this benefit has not always been reflected in phase III trials. For example, first-line treatment with erlotinib (150mgday?1) combined with standard platinum-based chemotherapy did not improve survival in the overall population of patients with advanced NSCLC; although never-smokers did experience a significant survival benefit in a post-randomisation analysis (Gatzemeier et al, 2004, 2005; Herbst et al, 2005).