Adjuvant Chemotherapy

Development of disease recurrence, either locally or systemically, after surgery or radiation or both

Presence and spreading of occult micrometastasis

Rationale: to treat micrometastatic disease at a time when tumor burden is a minimum, enhance potential efficacy of drug treatment

Adjuvant Chemotherapy

Several well-conducted randomized phase III clinical studies have documented the effectiveness of adjuvant chemotherapy in prolonging both disease-free and overall survival in cancer patients

Clinical end points:

àDisease-free survival

àOverall survival

Principles Governing the Use of

Chemotherapy (1)

Combination chemotherapy

àInteraction acts as initial stimulus

àSet off a cascade of events result in apoptosis (programmed cell death): p53, bcl-2

àGoldie-Coldman model: intrinsic drug resistance

Principles Governing the Use of

Chemotherapy (2)

Sequential use of drug combinations:

àNorton-Simon model: no two combinations were likely to be non-cross-resistant or have equal cell killing capacity

Optimal dose and schedule

àMaximal-tolerated dose

àshortest possible time necessary for recovery of bone marrow

Optimal duration of administration

Principles Governing the Use of

Chemotherapy (3)

Right indication

Right patient:

àAdequate organ function: bone marrow, hepatic, renal, cardiac, pulmonary

àPre-existing condition

àPerformance status