Antibiotic Effective for Ocular Lymphoma

MILAN, Italy, Oct. 3 -- A commonly used antibiotic effectively treats lymphoma of the soft tissue, lachrymal glands, and conjunctiva of the eye, according to researchers here.

In a prospective, non-randomized study, a three-week course of doxycycline at 100 mg twice daily induced a complete or partial response in 48% of patients, found Andres Ferreri, M.D., of the San Raffaele H Scientific Institute here.

The two-year failure-free rate -- where failure was defined as either progression or relapse -- was 66%, and 20 of the 27 patients had not progressed, Dr. Ferreri and colleagues reported in the Oct. 4 issue of the Journal of the National Cancer Institute.

The study was begun mainly because there was evidence of a link between ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas and the bacterium Chlamydia psittaci - a potentially causative link similar to that between gastric MALT lymphomas and Helicobacter pylori.

But Dr. Ferreri and colleagues found that the antibiotic appeared to work regardless of whether the patients were infected with C. psittaci: Seven of 11 carrying bacterial DNA had tumor regression, while six of the 16 without evidence of infection saw their lymphomas regress.

The finding raises two possibilities, the researchers said: either current methods of detecting the bacteria are not sensitive enough or there is some other bacterial cause of ocular MALT lymphoma that can be interrupted by doxycycline.

Dr. Ferreri and colleagues enrolled 27 consecutive patients seen at their Milan clinic, including 15 with a new diagnosis and 12 having had a relapse after standard treatment with either radiation or alkylating-based chemotherapy.

The study found:

• Six patients had a complete remission and seven had a partial response, defined as more than a 50% regression of measurable lesions.
• Another three patients had a minimal response - less than 50% regression of lesions - and nine had stable disease.
• Two patients progressed despite the treatment.

Response was slow and gradual, the researchers reported: The median time to the best response in the 16 patients who responded was six months, with a range from three to 36 months.

On the other hand, four patients had a complete remission within three months of the end of the treatment.

"Our prospective trial revealed that doxycycline is a fast, safe, and active treatment for (ocular adnexal MALT lymphoma) both at initial diagnosis and at relapse," the researchers concluded. The drug's combination of safety and activity make it a "valid therapeutic alternative" to standard care, they added.

But too many questions remain unanswered to suggest that doctors begin routinely treating such patients with doxycycline, commented Emanuele Zucca, M.D., and Francesco Bertoni, M.D., both of the Oncology Institute of Southern Switzerland in Bellinzona, Switzerland.

In an accompanying editorial, they argue that the study provides further support to the notion than an antigen response drives MALT lymphomas and that doxycycline leads to an objective in about half the cases involving the ocular adnexa.

But, they asked, is C. psittaci the causative agent? Are other bacteria at play? Is there a role for viral infection or chromosomal alterations?

"While doxycycline appears to be an easy-to-implement therapeutic approach, we strongly encourage all physicians to enroll patients in clinical prospective trials to help answer these questions," Drs. Zucca and Bertoni said.