Fifty-six full length studies were included (1606 patients, with 1448 patients evaluated for disease response).
Twelve agents (27% of agents tested) were identified that are now commonly used in the treatment of childhood cancers. Mean study size was 29 patients (range 7 to 84). Mean number of dose levels per trial was 5 (range 2 to 12). Gender was reported in 31 (55%) of studies. 26 studies were of children with either solid tumours or leukemia, 19 studies involved patients with solid tumours and 11 included only those with leukemia. Responses were observed in 33 studies (59%).
Overall response rates (CR or PR): high response rates were noted for ifosfamide (35%); iodine metaiodobenzylguanidine (33%); 6- diazo-5-oxo-L-norleucine ( 23%); and etoposide (21%).
Response (CR or PR) by tumour type: neuroblastoma (124 patients) 17.7%; osteosarcoma (123 patients) 2.4%; rhabdomyosarcoma (73 patients) 2.7%; Ewing's sarcoma/primitive neuroectodermal (72 patients) 4.2%; embryonal (56 patients) 7.1%; central nervous system (191 patients) 5.2%; other soft tissue sarcomas (185 patients) 9.2%; acute lymphoblastic leukemia (291 patients) 8.6%; acute myelogenous leukemia (112 patients) 11.6%; unknown type of leukemia (30 patients) 0%; and total leukemia (433 patients) 8.7%.
Doses achieving objective response were specified for 52 of 61 patients with solid tumours and 36 of 38 with leukemia. Mean doses resulting in response were 91% of MTD for solid tumours and 104% for leukemia.
Overall death rate on study was 7.0%. Toxic death reported in 12 (0.7%) patients. Mean dose resulting in TD was 158% of MTD (range 100% to 300%). Death due to aplasia reported in 11 (0.7%) patients. Progressive disease resulted in death of 90 (5.6%) patients. 2.7% (43 patients) of entered patients were treated at/above 150% MTD, and 5 of these died from drug toxicity.
4 drugs had a higher number of TD than responses (2'- doexycoformycin, homoharringtonine, interleukin-2, and indicine). Over time there was a statistically significant trend of fewer dose levels per trial and fewer patient per trial were reported. 1978 to 1984; number of drugs 8; number of trials 8; patients entered/evaluated 313/293; CR or PR rate 5.5%; death rate 6.0%, toxic death rate 0.9%.
1985 to 1989; number of drugs 22; number of trials 19; patients entered /evaluated 589/535; CR or PR rate 6.0%; death rate, 8.3%; toxic death rate 0.5%.
1990 to 1996 (3): number of drugs 26; number of trials 22; patients entered/evaluated 689/620; CR or PR rate 10.3%; death rate 6.6%; toxic death rate 0.9%.