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Adjuvant radiotherapy is the rule after conservative surgery for breast cancer. Furthermore, an anthracycline-based chemotherapy is recommended in node-positive patients and in poor prognosis tumors. The optimal schedule of treatment has yet to be determined, but ideally, none of these therapeutic modalities should be delayed. We have therefore conducted a feasibility trial using post-operative concurrent chemoradiation therapy with an anthracenedione. Between May 1990 and October 1994, 154 patients with stage I or II breast cancer who had benefited of either limited or radical surgery were treated with adjuvant concurrent chemoradiotherapy. Radiotherapy consisted of 50 Gy in 25 fractions over 5 weeks to the chest wall or the breast, and to the supraclavicular and internal mammary lymph nodes. When indicated, a boost of 15 Gy was then delivered to the primary tumor bed (n = 75). Starting on the first week of radiotherapy, combined chemotherapy with 5-fluorouracil, mitoxantrone, and cyclophosphamide was administered at 21-day intervals, for 4 to 6 cycles. Compliance to therapy was excellent. Median radiotherapy dose was 49.5 Gy to the chest wall or breast, and to the lymph nodes, and 14.2 Gy to the tumor bed. Chemotherapy was given at full dose in over 80% of the cases and the 21-day interval between cycles was respected in 31%. In 45% of the cases, a 28-day interval was required due to toxicity, and at least one interval longer than 28 days was necessary in the remainder of the patients. Main toxicities were nausea and vomiting (20.8%) and grade 3-4 neutropenia (12.3%). Grade 1 cutaneous toxicity occurred in 62.3% of the cases, and severe grade 3 radiation dermatitis requiring temporary interruptions of therapy in 4.5%. With the exception of one case of grade 3 acute cardiac toxicity, there was no other severe side-effects. In conclusion, this pilot study demonstrates the feasibility of concurrent chemoradiation therapy with an anthracenedione for stage I and II breast cancer in the adjuvant setting. Whether this approach compares favorably with standard sequential therapy in terms of long-term results remains to be determined and should be assessed in a phase III trial.

The filaria Monanema martini with skin-dwelling microfilariae induces in its natural murid hosts lesions similar to those in human onchocerciasis. This was demonstrated by histo-pathological studies but it appeared useful to evaluate the model by a clinical investigation. An ophthalmological analysis was performed on the two species of hosts, inoculated by one, two, or multiple doses of larvae, and with infections of at least one year duration. A total of 140 eyes was examined (anterior and posterior segments). We established a system for enumerating the different types and severities of lesions. We prepared a file for each eye and attempted to quantify our observations. The significant lesions were different in the two host species. In Arvicanthis niloticus, in which motile microfilariae were seen in the anterior segment, punctate keratitis was predominant. In Lemniscomys striatus, the posterior segment showed complete chorioretinal atrophy, similar to the final stage of onchocercal chorioretinitis in humans. M. martini represents in its natural hosts two complementary models for the study of the pathogenesis and treatment of human onchocerciasis.

Histo-pathological analysis of the eyes, ears, skin and associated skeletal muscles of the back of 14 animals infected with a filarioid worm with dermal microfilariae, Cercopithifilaria johnstoni: seven Rattus fuscipes, of which four were naturally infected, two marsupials, Perameles nasuta and Isodon macrourus, and five R. norvegicus. This filarioid nematode induces skin and eye lesions in all the infected animals. These lesions are similar to those described earlier with other filarioid species with dermal microfilariae, such as Monanema martini and Onchocerca volvulus; the pathogeny is similar: microfilariae live inside the lymphatic vessels and their accidental exit gives rise to a localized inflammatory reaction leading to fibrosis. C. johnstoni is particularly interesting because it may be adapted to the laboratory rat, and because the ocular lesions are severe.