Abstract
Most patients with neuroblastoma (NB) achieve some response to aggressive chemotherapy. However, some of them have relapse and the tumors subsequently become refractory to drugs. The development of resistance to chemotherapy is a major problem in the treament of NB. We have examined the development of resitance to a high dose of Cyclophosphamide (CPM) in human NB growing as a xenograft (HNX) in nude mice. Three types of HNX (CH-NBI, CH-N-1, CH-NB-4) were treated in consecutive passages with a single dose of 250mg/kg CPM. At each passage the first treated tumor to regrow was transplanted into 10 fresh mice. Of these mice half were treated and half served as controls. This procedure was repeated six times. Growth curves were plotted and the time taken for treated and control groups to double in volume was obtained. Tumor growth delay (TGD) was calculated as the difference between these values. Various changes in TGD produced by repeated CPM treatments were observed in three HNX. TGD dropped from 10.7 to 7.1 days in CH-NB-4 (p < 0.05) at the 2nd transplant and from 9.6 to 7.5 days in CH-N-1 at the 5th transplant and no further decrease was observed by additional treatment in any tumor. TGD was 5.3 days in CH-NB-I at the 1st transplant and no decrease was observed by additional treatment. Treatment with CPM resulted in a rapid reduction in responsiveness to CPM in two HNX but no reduction was observed in one HNX which was considered to have primary resistance to CPM.
