Researchers from the UK have reported that patients with locally advanced bladder cancer treated with concomitant carbogen, nicotinamide, and radical accelerated radiotherapy have a 13% improved three-year survival compared with patients treated with radiotherapy alone. The details of this Phase III randomized trial were presented at the 2009 meeting of the American Society of Therapeutic Radiology and Oncology (ASTRO) in the first week of November.[1]

Patients with advanced bladder cancer are often treated with radiotherapy alone. The administration of neoadjuvant chemotherapy has been reported to reduce the risk of death by 13% and improve the five-year survival by approximately 5% in patients receiving surgery, radiation therapy, or the combination of radiation therapy and surgery.

Another approach to improving the results of radiotherapy for treatment of bladder cancer is to add hypoxia-modifying agents. One method of improving oxygenation is to add carbogen, which is an inhaled mixture of 98% oxygen and 2% carbon dioxide. A second approach is the administration of nicotinamide, which increases blood flow, thereby theoretically increasing oxygenation of tumor tissue.  An early study added carbogen, nicotinamide, or both to radical accelerated (hypofractionated) radiotherapy for the treatment of patients with locally advanced bladder cancer with promising results and good toleration.[2] Two other Phase II reports documented that this combined approach did not increase treatment-related toxicity.[3] [4]

Preliminary results of a randomized controlled trial comparing radiotherapy alone to radiotherapy plus concommitant carbogen and nicotinamide in patients with locally advanced bladder cancer were published in Radiotherapy and Oncology in April of 2009.[5] This study has now accrued 333 patients with advanced bladder cancer. All patients received radiotherapy to a total dose of 55 Gy in 20 fractions over four weeks or 64 Gy in 32 fractions in 6.5 weeks. Patients were randomly allocated to receive radiotherapy alone or radiotherapy with carbogen and nicotinamide. Carbogen was inhaled before and during radiotherapy. Oral nicotinamide was administered 1.5-2 hours before radiotherapy.

The following table summarizes the main findings of this trial:

Toxicities between the two groups were comparable. These authors concluded that there was a 13% survival advantage at three years for patients receiving carbogen and nicotinamide.

Comments: This is a novel approach to the treatment of locally-advanced bladder cancer. It will be of interest to see if this technique is added to neoadjuvant chemotherapy, which appears to be a more standard approach to treating locally advanced bladder cancer.

References:
[1] Hoskin P, Rojas A, Bentzen S, et al. Randomized phase III trial of radical radiotherapy with concurrent carbogen and nicotinamide in locally-advanced bladder cancer. International Journal of Radiation Oncology Biology Physics. 2009;75:issue 2, supplement, abstract 7.