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Clinical Applications of Antineoplastic Chemotherapy

Chemotherapy

5th-6th decades of 20th century

Subsequent integration into treatment protocols

Limitations due to resistance, toxicity

Understanding of mechanisms through which the drugs work

History

Paul Erlich coined the term chemotherapy

George Clowes at Roswell Park developed rodent lines to test potential drugs

Alkylating agents – First class

Product of a secret gas programme by USA

1943 use in Hodgkin’s lymphoma

Sidney Farber – folic acid analogs

Cure of childhood leukaemia and HD-1960

Work with solid tumors – disappointing

Nearly 90% drug cures occur in 10% cancer types

Felt that this was related to tumor characteristics and drug resistance

Tumor features

Cancer cells do not divide at faster rate than normal cells

Greater number of cells dividing

Slow growing tumors – less responsive

Faster growing tumors – more responsive and curable

Highly aggressive cancer – almost incurable

e.g. Non-Hodgkin’s lymphoma

Diffuse large cell lymphoma - curable in advanced stages (more aggressive)

Indolent lymphoma - responds to treatment but likely incurable in advanced stages (low grade)

Increase in growth fraction - negative response to Rx-? emergence of resistance

Normal cells

Never develop resistance

Resistance of tumor cells associated with sensitivity of normal cells

Bone marrow and GIT cells are most vulnerable

Chemotherapy options

Induction for advanced disease

As adjunct to local treatment

Primary treatment for localized disease when local treatment is not possible

Direct instillation to sanctuary sites or site direct perfusion (CNS therapy for acute leukaemia)

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