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ARCADIAN: Atovaquone with Radical ChemorADIotherapy in locally Advanced NSCLC

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Primary Publication

Pending

Lay Summary

Atovaquone with Radical ChemorADIotherapy in locally Advanced NSCLC – LAY SUMMARY

Cancer cells inside solid tumours divide and grow quickly, using up oxygen in the process. Tumours also typically develop abnormal blood vessels, which makes it difficult to deliver enough oxygen. Because of these factors, some areas within tumours become very low in oxygen. In cancer cells, this triggers abnormal internal pathways to be activated, which make tumours spread more quickly and become resistant to treatment. Low oxygen is also a problem for patients having radiotherapy, because oxygen is required inside the tumour to create the toxic chemicals that help kill the cancer cells. Therefore, there is a need to find ways to increase the oxygen levels inside tumours in order to improve the impact of cancer treatments.

Previous research has shown that a drug used to treat certain infections, called atovaquone, can increase the amount of oxygen in cancer cells. Therefore, the ARCADIAN clinical trial aimed to find out if atovaquone could be safely given to cancer patients at the same time as radiotherapy. This clinical trial focused on patients with a type of cancer called non-small cell lung cancer (NSCLC) who were being treated with chemotherapy and radiotherapy at the same time (chemoradiotherapy).

To find out whether the combination of atovaquone and chemoradiotherapy is safe, initial patients enrolled in the trial were given a low dose of atovaquone alongside their standard treatment. Data on any side effects experienced was collected, and subsequent patients were only given higher doses if safe to do so. This is called a dose escalation study and allows researchers to find the best dose to give.

The key aims of this study were to find out:

  • If it is safe to combine atovaquone with chemoradiotherapy
  • The best dose of atovaquone to give with chemoradiotherapy
  • The side effects of giving atovaquone with chemoradiotherapy

Researchers were also interested in finding out whether there is a way to measure the level of oxygen in patient’s tumours from a blood or tumour sample, rather than via a special scan (which measures tumour oxygen level, but is expensive). This could help to identify patients with low tumour oxygen levels who might benefit most from taking atovaquone alongside their standard cancer treatment in the future.

A total of 21 patients were enrolled on the trial. Each was allocated one of four doses of atovaquone (450, 600, 675 or 750 mg) to take in both the morning and the evening for up to 3 weeks before starting chemoradiotherapy, and then alongside their chemoradiotherapy. All patients stopped taking atovaquone when their course of chemoradiotherapy treatment was complete.

 

Standard chemoradiotherapy for these patients consisted of the following:

  • Radiotherapy (every week day for 6 ½ weeks) 
  • Cisplatin (in weeks 1 and 4)
  • Vinorelbine (in weeks 1, 2, 4 and 5)

No severe side effects were identified, therefore the trial showed that it is safe to take atovaquone at the same time as having chemoradiotherapy. The best dose of atovaquone to take was the highest dose investigated (750 mg, twice a day). This dose was taken by 15 participants in the trial and was shown to be safe in combination with chemoradiotherapy.

Over half of the participants completed the two scans required to measure change in low tumour oxygen level, before and after atovaquone. Some patients did not complete both scans, for example because low tumour oxygen level was not detected on the first scan. Overall, these demonstrated an increase in oxygen levels in tumours after taking atovaquone. Of the alternative methods tested, neither represented a reliable substitute for scanning.

In summary, this means that the combination of atovaquone with chemoradiotherapy is safe and warrants further trials to determine whether this combination improves patient outcomes after treatment. Since atovaquone is not lung-cancer specific, it has the potential to improve the impact of therapy for other types of cancers too.

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