Approximately 1.6 million new cases of cancer are expected to be diagnosed in the United States in 2013. Many patients diagnosed with cancer will eventually require support from a family caregiver. In fact, family caregivers form the foundation of the health care system in the United States, supporting advances in treatment such as multimodality treatment protocols given in outpatient and home settings.
Definition: Who Is the Caregiver?
Also referred to as informal caregivers, family...
Standard treatment options for maintenance therapy include the following:
Central nervous system (CNS)-directed therapy is provided during premaintenance chemotherapy by all groups. Some protocols (Children's Oncology Group [COG], St. Jude Children's Research Hospital [SJCRH], and Dana-Farber Cancer Institute [DFCI]) provide ongoing intrathecal chemotherapy during maintenance, while others (Berlin-Frankfurt-Münster [BFM]) do not. (Refer to the CNS-Directed Therapy for Childhood Acute Lymphoblastic Leukemia section of this summary for specific information about central nervous system therapy to prevent CNS relapse in children with ALL who are receiving postinduction therapy.
Once remission has been achieved, systemic treatment in conjunction with CNS sanctuary therapy follows. The intensity of the postinduction chemotherapy varies considerably depending on risk group assignment, but all patients receive some form of intensification following achievement of remission and before beginning maintenance therapy. Intensification may involve use of the following:
Intermediate-dose or high-dose methotrexate (1–5 g/m2) with leucovorin rescue or escalating-dose methotrexate without rescue.[1,2,3,4]
Drugs similar to those used to achieve remission (reinduction or delayed intensification).[1,5]
Different drug combinations with little known cross-resistance to the induction therapy drug combination including cyclophosphamide, cytarabine, and a thiopurine.
In children with standard-risk ALL, there has been an attempt to limit exposure to drugs such as anthracyclines and alkylating agents that may be associated with an increased risk of late toxic effects.[10,11,12] For example, regimens utilizing a limited number of courses of intermediate-dose or high-dose methotrexate as consolidation followed by maintenance therapy (without a reinduction phase) have been used with good results for children with standard-risk ALL.[2,3,11] Similarly favorable results for standard-risk patients have been achieved with regimens utilizing multiple doses of L-asparaginase (20–30 weeks) as consolidation, without any postinduction exposure to alkylating agents or anthracyclines.[7,13]
Evidence (intensification for standard-risk ALL):
Clinical trials conducted in the 1980s and early 1990s demonstrated that the use of delayed intensification improved outcome for children with standard-risk ALL treated with regimens using a BFM backbone.[14,15,16] The delayed intensification phase on such regimens, including those of the COG, consists of a 3-week reinduction (including anthracycline) and reconsolidation containing cyclophosphamide, cytarabine, and 6-thioguanine given approximately 3 months after remission is achieved.[1,14,17]
A Children's Cancer Group study (CCG-1991/COG-1991) for standard-risk ALL utilized dexamethasone for induction and a second delayed intensification phase. This study also compared escalating intravenous (IV) methotrexate in conjunction with vincristine versus a standard maintenance combination including oral methotrexate given during two interim maintenance phases.[Level of evidence: 1iiDi]
A second delayed intensification phase provided no benefit in patients who were rapid early responders (M1 marrow on day 7).
IV methotrexate produced a significant improvement in event-free survival (EFS), which was primarily a result of a decreased incidence of CNS relapse.