The clinical effect of bleomycin on lung cancer was studied and pulmonary fibrosis as aside effect was discussed clinically and pathologically.
Nine cases with lung cancer were treated with bleomycin. The clinical effect of bleomycinas reduction of tumor size or disappearance of atelectasis was seen in three cases with squamouscell carcinoma, two cases with large cell anaplastic carcinoma and one case with adenocarcinoma.Any clinical effect was not seen in the other three cases including two with adenocarcinomaand one with squamous cell carcinoma. In two resected cases marked necrosis anddegeneration of cancer cell were shown histologically, which were considered to be the effectof bleomycin.
The clinical course of case 1 with a large cell anaplastic carcinoma of peripheral type waspresented, showing a marked reduction of tumor size by bleomycin therapy combined withmitomycin C and 5-fluorouracil. It was indicative of much effect on the tumor with less sideeffect by the combination therapy with other anti-tumor drugs.
Among the side effects of bleomycin anorexia and fever were seen in more than half ofthe cases. Pigmentation on the face and hand and falling out of the hair were also seen in somecases.
Above all, however, the most significant side effect was pneumonitis-like or fibrotic changeof the lung on X-ray, which occurred slightly in two cases and remarkably in one case.
In case 3 with remarkable change of the lung on X-ray due to bleomycin, the process in thelung was clarified histologically in its early stage by lung biopsy and in its advanced stage by pneumonectomy. In this case the administration of bleomycin was discountinued when the dosagebecame to 195 mg, because the chest X-ray showed small nodular and reticular shadows in theentire lung field coexistent with elevation of the diaphragm, while tumor showed reduction insize with disappearance of aletelectasis of the left lower lobe. The vital capacity was reducedto 1, 770 ml (53%), which had been 3, 000ml (90%) before treatment. Eleven days later understeroid hormone therapy the open lung biopsy was performed. Numerous small nodules wereseen in the surface of the lung and several spieces of the lung were biopsied. Pneumonectomywas performed one week after the biopsy since X-ray findings and lung function had been fairlyimproved under the treatment with steroid hormone. At the time of pneumonectomy the nodulesin the lung surface had almost disappeared and subpleural induration was present.
Histological findings of the biopsied specimen in the early stage of the process showedremarkable edematous change of the pleura, the subpleural inter-lobular septum and the subpleuralalveolar wall; in these areas infiltration of polymorphonuclear leukocytes to the venuolewall, thickening of the venule wall due to deposit of hyalinous substance and dilation of thecapillary were seen. The proliferation of the fibroblast was found in some parts of the edema.These findings had already disappeared in the resected lung, while marked proliferation ofconnective tissue of the alveolar wall was seen in the subpleural area with collagenous thickening of the intima of the venule.
Although X-ray finding of the remaining lung showed no change, the lung function wasdecreased gradually and died from respiratory insufficiency seven months after operation.
The lung change due to bleomycin, therefore, has a possibility of rapid transformationfrom reversible to irreversibee process on the histological point of view.
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