According to results from the Phase II CO-HO-RT (Concomitant HOrmono-RadioTherapy) study, letrozole can be safely delivered concomitantly with radiotherapy, shortly after surgery for early stage breast cancer.

According to the authors, preclinical studies have suggested that the aromatase inhibitor letrozole may have a radiosensitising effect.  They therefore designed this trial to determine whether this effect occurs in vivo, by comparing adjuvant concomitant radiotherapy and letrozole with sequential radiotherapy and letrozole in early breast cancer.  

A total of 150 postmenopausal women with early-stage breast cancer were randomised to open-label treatment with concurrent radiotherapy and letrozole (n=75) or sequential radiotherapy and letrozole (n=75), following breast-conserving surgery.  The majority of participants (61% in each group) did not receive adjuvant chemotherapy.  Letrozole was given at a dose of 2.5mg daily for five years.  The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced grade 2 or worse toxic effects of the skin. 

The main findings were as follows:

• 31 patients in the concurrent group and 31 in the sequential group had any grade 2 or worse skin-related toxicity (most commonly dermatitis) during radiotherapy and within the first 12 weeks after radiotherapy.
• At a median follow-up of 26 months (range 3—40), two patients in each group had grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis).

Although this study was not formally designed to directly compare the two groups, the authors conclude that concurrent and sequential administration of letrozole with adjuvant radiotherapy after breast-conserving surgery may result in similar acute and late skin-related adverse events.  They note that longer follow-up is required to assess whether there is any difference in clinical outcomes between the two, and to investigate cardiac side-effects.