Studies on the Treatment of Malignant Tumors With Fibroblasts Inhibiting Agents Basic and Clinical Studies of Chloroquine Derivatives. (1)

Followings are the results derived from the treatment of animal and human cancers with a fibroblasts inhibiting agent such as chloroquine, based on the unique idea of ours. 1). In implanted tumors of animals, the effect was noted in Bashford cancer and Brown-Pearce cancer relatively rich in connective tissue in terms of life prolongation, an inhibition of tumor growth and of decrease of liver catalase activity, an improvement of iron metabolism, an enlargement of necrotic area in histology, an inhibition of connective tissue conponents, and a decrease of acid mucopolysaccharides. A tendency for a decrease of amount and cell numbers of ascites was almost the only effect noted in Ehrlich cancer, Yoshida sarcoma, and MH 134 poor in connective tissue. 2). 75 cases of humau cancer were treated with this agent and among these 75 the effect was evaluated in 40 cases with definite histological diagnosis in respects with subjective and objective improvement. It was effective in 28 cases, resulted failure in 11 cases, and gave an obscure result in 1 case. Cases which were treated for more than 2m onths never resulted in therapeutic failure, indicating that the agent was somehow effective for all cases but those in the last stadium. In respect with organs involved, the effect was most prominent in lung cancer and urinary bladder cancer, somewhat less in gastric cancer, and often seen in carcinomatous peritonitis and many other advanced cancers. This effect was noted in a comparatively short period in terms of subjective improvement, regression in size of tumors in a number of cases, a decrease of serum lactic acid dehydrogenase, and improvement of general condition, a tendency for necrosis of tumor and an inhibition of interstitium. 3). The above results indicate that the agent is more effective for tumors rich in connective tissue and that it's secondary effect on tumors through the inhibition of interstitial connective tissue is considered as the operative mechanism of chloroquine against malignant tumors, but it's anti-inflammatory effect and generalized influence on hosts are to be taken into consideration. The agent is indicated in inoperable cases, postoperative relapse, or prior and following an operation. A search for stronger fibroblasts inhibiting agents and an evaluation of combined therapy with so called anti-cancer agents are being made and that with mitomycin C is giving a fairly promising result