Phase II study of cisplatinum and carboplatinum (CACIS) combination in advanced stage neuroblastomas

Platinum derivatives are, among others (cyclophosphamide, etoposide, doxorubicin), the most active drugs in neuroblastomas. As the combination of carboplatin (CBDCA) with cisplatinum (CDDP) was proven effective in some carcinomas, we proposed it as a second-line therapy in neuroblastoma.

Nineteen children with neuroblastoma and primary refractory disease (seven cases) or relapse either untreated (eight cases) or resistant to second-line therapy (four cases), were treated with cisplatinum and carboplatinum (CACIS) combination. All but one patient had previously received CDDP (median 400: 200 to 1,200 mg/m2) and 15 out of 19 had also received CBDCA (median 1,600:800 to 5,000 mg/m2). Twelve had previously received intensification with megatherapy. The CACIS regimen included CBDCA (100 mg/m2/day as a 1-hour infusion, for 4 days) and simultaneous CDDP (25 mg/m2/day as a 3-hour infusion, for 4 days).

Eight out of 19 patients (42%) achieved a partial response with a duration of response of 3 to 12 months (median 6). No patient achieved a complete response. The toxicity was mainly hematological, though one patient died after two courses of an interstitial pneumonia of unknown origin. Only one patient developed alopecia. The renal toxicity was low.

The CACIS regimen is an effective combination of platinum derivatives. It may be proposed as second line protocol, especially for children with neuroblastoma who relapse after megatherapy.