Adjuvant cisplatin for NSCLC raises non-cancer mortality risk

By Afsaneh Gray, medwireNews Reporter

Re-analysis of data from the International Adjuvant Lung Cancer Trial (IALT) indicates that cisplatin-based adjuvant chemotherapy increases the long-term risk of non-cancer mortality in patients with non-small-cell lung cancer (NSCLC).

However, the chemotherapy also reduced the risk of local cancer relapse and of non-brain metastases, with the scientists estimating that more than half of patients may benefit from the treatment, whereas the harmful effects on non-cancer mortality only became significant after 5 years.

Nonetheless, lead author Federico Rotolo (Service de Biostatistique et d’Epidémiologie, Villejuif, France) and colleagues advise: “Detailed long-term follow-up is strongly recommended for all patients in randomized trials evaluating adjuvant treatments in NSCLC.”

The researchers looked at data from 1687 patients enrolled into the IALT from across 132 centres and followed-up for a median of 7.5 years. Event-history methodology was used to estimate the effects of adjuvant chemotherapy on the risks of local relapse of disease, distant metastasis and death.

The results showed that adjuvant chemotherapy was highly effective at preventing local relapses (hazard ratio (HR)=0.73) and non-brain metastases (HR=0.79), but had no impact on the risk of brain metastases (HR=1.1).

Local relapses occurred mostly during the first 5 years, at a rate of 28% compared with 32% at 10 years. The risk for death increased by a significant 26-fold after local relapse.

The rate of distant metastases was 33% at 5 years and 38% at 10 years. Both the 202 cases of brain metastases and the 487 cases of non-brain metastases had a large effect on the risk of death, with HRs of 38 and 40, respectively.

The effect of treatment on the likelihood of non-cancer mortality was not significant during the first 5 years of follow-up. Thereafter, however, chemotherapy raised the risk of non-cancer mortality risk by a significant 3.6-fold even though the anti-cancer benefit was still ongoing.

But the researchers emphasise that this harmful effect potentially concerned only 2% of patients after 8 years.

The most plausible explanation for the late over-mortality is a long-term toxic effect of cisplatin suggested by published results in NSCLC and other cancers”, Rotolo and colleagues say.

Nevertheless, they conclude in the Annals of Oncology, that their study involved small numbers of non-cancer deaths and urge further follow-up of future NSCLC adjuvant chemotherapy trials.

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