Anal submucosal injection: a novel modality for the treatment of advanced rectal cancer

To investigate the efficacy of methotrexate (MTX) submucosal anal injection in the treatment of advanced rectal cancer.

Thirty-six patients (age 36-66 years; 21 men, 15 women; 20 patients with stage T3N1M0 and 16 with T4N1M1 rectal cancer) were injected with MTX in the anal submucosa. A comparative group of eight patients (age 38-62 years: five men, three women; four with T3N1M0 and four with T4N1M1 rectal cancer) was injected with MTX intravenously. The dose in both groups was 100 mg every 5 days for five consecutive doses and the course was repeated at 3-week intervals. MTX serum and tumour concentrations were estimated 30 and 60 min after MTX injection. The patients received MTX as outpatients.

In the anal group, six of 20 patients with T3 tumour showed complete tumour regression and were alive 28-46 months after the start of the treatment. Partial response occurred in 25 patients: 14 of stage T3 and 11 of T4. The 14 T3 patients underwent combined excision operation and 9/14 were alive 26-68 months from the time of operation. Five of the 16 T4 patients showed tumour and metastatic progression. Mild toxicity occurred in six of 36 patients while the haematological reserve was unchanged in all the patients. All eight patients in the parenteral group showed progress of the malignant lesions under treatment and toxic manifestations were so severe that the treatment had to be interrupted. The MTX concentration in serum was significantly higher after parenteral than after anal injection, while in tumour tissue it was higher after anal administration.

The results show that MTX submucosal anal injection is effective in treatment of T3 rectal cancer due to high MTX concentration in the tumour. Toxicity was mild owing to low level of serum MTX. The anal route of administration is safe, well tolerated and can be used on an outpatient basis.