Intermediate Risk Group

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The intermediate-risk group (Table 18-8) consists of patients with:

1. INSS stage 3, younger than 1 year, with nonamplified MYCN, favorable or unfavorable histology

2. INSS stage 3, older than 1 year, nonamplified MYCN and favorable Shimada histology

3. INSS stage 4 infants, younger than 1 year, with nonamplified MYCN and favorable or unfavorable Shimada histology

4. INSS stage 4S infants, younger than 1 year, with nonamplified MYCN, favorable or unfavorable histology and DNA index of 1

5. INSS stage 4S infants, younger than 1 year, with nonamplified MYCN, unfavorable Shimada pathology.

Patients with intermediate-risk neuroblastoma have a reported estimated 3-year survival of 75-98%.

Treatment

Surgery is indicated as described under general treatment modalities earlier in this chapter. Table 18-9 describes various induction chemotherapy and response rates from the Pediatric Oncology Group (POG), the Children's Cancer Group (COG), and the European Neuroblastoma Study Group (ENSG).

The recent cooperative COG, based on clinical INSS stage, age, and selected biologic features such as MYCN, Shimada histopathology, and ploidy, has developed a chemotherapy regimen designed to maintain or improve event-free survival of previous studies and to minimize acute and long-term morbidity for this group of patients. This regimen uses four of the most active agents in neuroblastoma treatment (carboplatin, etoposide, cyclophosphamide, and doxorubicin). Patients with intermediate-risk neuroblastoma and favorable biology get one course of four cycles of chemotherapy, and patients with unfavorable biology get two courses (eight

Table 18-9. Induction Chemotherapy Regimens and Response Rates from Pediatric Oncology Group, Children's Cancer Group, and European Neuroblas-toma Study Group.

POG-8742 (regimen 1) Days 1-5, CDDP 40 mg/m2/day 77

Days 2-4, VP-16 100 mg/m2/day Alternating every 21 days with Days 1-7, CPM 150 mg/m2/day (PO) Day 8, DOX 35 mg/m2 Total of 5 cycles OR

CCG-3891 Day 1, CDDP 60 mg/m2 78

Day 3, DOX 30 mg/m2 Days 3 and 6, VP-16 100 mg/m2 Days 4 and 5, CPM 900 mg/m2 Repeat every 28 days x 5 cycles OR

ENSG-3C Days 1-5, CDDP 40 mg/m2/day 55

Days 1-5, VP-16 100 mg/m2/day Days 21-23, Ifos 3 g/m2/day Day 21, VCR 1.5 mg/m2 Day 23, DOX 60 mg/m2 Repeat 3-4 weeks x 4 cycles

Abbreviations: CDDP, cisplatin; CPM, cyclophosphamide; CR, complete response; DOX, doxorubicin; PR, partial response; VCR, vincristine; VP-16, etoposide; Ifos, ifosfamide.

aAll drugs are given intravenously unless noted otherwise.

bResponses all include surgery and 5-6 months of chemotherapy.

Adapted from Matthay KK, Castleberry RP. Treatment of advanced neuroblastoma: the U.S. experience. In: Brodeur GM, Sawada T, Tsuchida Y, et al., editors. Neuroblastoma. Amsterdam: Elsevier Science, 2000;437-52, with permission.

cycles). Each cycle is given every 3 weeks. For the details of this chemotherapy, see doses and schema as described next.

Treatment for Patients with Intermediate-Risk Favorable Biology

For children <1 year of age or who are <12 kg in weight, the doses of chemotherapy are adjusted and given as milligrams per kilogram. Each of four cycles is given at 3-week intervals.

1. Carboplatin 560 mg/m2 or 18 mg/kg IV over 1 hour for 1 day

2. Etoposide 120 mg/m2 or 4 mg/kg IV over 2 hours daily for 3 days

3. Cyclophosphamide 1000 mg/m2 or 33 mg/kg over 1 hour daily for 1 day

4. Doxorubicin 30 mg/m2 or 1 mg/kg IV over 60 minutes daily for 1 day.

The various drugs are given on the following days of the course.

Cycle number

Day

Agents

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