High-Dose ICE (Ifosfamide, Carboplatin, Etoposide) Helps in Neuroblastoma Salvage

September 21, 2012

NEW YORK (Reuters Health) Sep 19 - High-dose ifosfamide, carboplatin and etoposide (HD-ICE) is an effective treatment for refractory or relapsed neuroblastoma, according to a new retrospective study from Memorial Sloan-Kettering Cancer Center in New York City.

The risk of major non-hematological toxicity was low, Dr. Brian H. Kushner and his colleagues reported September 5th online in Cancer.

Many patients with resistant neuroblastoma have gone for a prolonged period without receiving platinum based drugs, which have an "appealing" lack of cardio-, hepato- or gastrointestinal toxicity, Dr. Kushner and his team note. The lack of ototoxicity with ICE, and the acceptable myelosuppression risk, also suggest that high dosing is feasible, the authors note.

Their analysis included all 74 children treated with HD-ICE for resistant, high-risk neuroblastoma at Memorial between October 2004 and March 2012. Prior therapy included high-dose cyclophosphamide and etoposide in all cases, high-dose carboplatin and/or cisplatin in 69 patients (with lower dose cisplatin or carboplatin in the other five), and ifosfamide in seven patients.

On days one through five of the salvage therapy, patients received 2,000 mg/m2 of ifosfamide plus the same dosage of Mesnex (a compound given to reduce the risk of hemorrhagic cystitis with ifosfamide). They also received 500 mg/m2 of carboplatin on days one and two; and 100 mg/m2 of etoposide on days one through five.

Patients with a persistent platelet count below 100,000/microliter received peripheral blood stem cells (PBSC) 72 hours after HD-ICE. Altogether, 37 cycles were followed by PBSC infusion, resulting in uncomplicated hematologic recovery in all patients.

Granulocyte-colony-stimulating factor treatment began 24 hours after the completion of treatment, for the patients who did not require PBSC, or 24 hours after PBSC rescue.

The 74 patients received a total of 92 cycles.

Among the 17 being treated for a new relapse, nine (53%) showed a major response and 14 (82%) had disease regression. Four of the 26 patients with refractory neuroblastoma (15%) had major responses, while 13 (50%) showed disease regression. Thirty-four patients were treated for disease that progressed during chemotherapy; one of these patients (3%) showed a major response and 12 (35%) had disease regression.

Most patients were eventually hospitalized for infection or febrile neutropenia. Grade 3 toxicities included encephalopathy in two patients, mucositis in three patients, elevated liver enzymes in three patients, and gastroenteritis in one patient. Patients developed blood-borne bacterial infections in 24 cycles.

"The large experience reported herein resulted from our turning to HD-ICE in a variety of different clinical situations among the many NB patients who were referred to MSKCC for salvage therapy," Dr. Kushner and his colleagues write.

"We conclude that, in patients with high-risk NB, turning to HD-ICE for salvage or consolidative therapy is an attractive option because of noncross-resistance with widely used retrieval regimens," they add. "The risk of excessive morbidity from nonhematologic toxicity is low and therefore acceptable. PBSC support is unnecessary when hematologic reserve is intact."

SOURCE: http://bit.ly/RxDJCe

Cancer 2012.