Objective: To examine the pre-clinical and clinical evidence for the use of oxaliplatin
or paclitaxel salvage chemotherapy in patients with cisplatin-resistant cancer.
Methods: Medline was searched for 1) Cell models of acquired resistance reporting
cisplatin, oxaliplatin and paclitaxel sensitivities and 2) Clinical trials of single agent
oxaliplatin or paclitaxel salvage therapy for cisplatin/carboplatin-resistant ovarian
cancer. Results: Oxaliplatin - Oxaliplatin is widely regarded as being active in
cisplatin-resistant cancer. In contrast, data in cell models suggests that there is crossresistance
between cisplatin and oxaliplatin in cellular models with resistance levels
which reflect clinical resistance (<10 fold). Oxaliplatin as a single agent had a poor
response rate in patients with cisplatin-resistant ovarian cancer (8%, n=91).
Oxaliplatin performed better in combination with other agents for the treatment of
platinum-resistant cancer suggesting that the benefit of oxaliplatin may lie in its more
favourable toxicity and ability to be combined with other drugs rather than an
underlying activity in cisplatin resistance. Oxaliplatin therefore should not be
considered broadly active in cisplatin-resistant cancer. Paclitaxel – Cellular data
suggests that paclitaxel is active in cisplatin-resistant cancer. 68.1% of cisplatinresistant
cells were sensitive to paclitaxel. Paclitaxel as a single agent had a response
rate of 22% in patients with platinum-resistant ovarian cancer (n = 1918), a significant
increase from the response of oxaliplatin (p<0.01). Paclitaxel-resistant cells were also
sensitive to cisplatin, suggesting that alternating between agents may be beneficial.
Studies of single agent paclitaxel in platinum-resistant ovarian cancer where patients
had previously received paclitaxel had an improved response rate of 35.3% n=232
(p<0.01), suggesting that pre-treatment with paclitaxel improves the response of
salvage paclitaxel therapy.
Conclusions: Cellular models reflect the resistance observed in the clinic as the cross
resistant agent oxaliplatin has a lower response rate compared to the non-cross
resistant agent paclitaxel in cisplatin-resistant ovarian cancer. Alternating therapy
with cisplatin and paclitaxel may therefore lead to an improved response rate in