Adjuvant chemotherapy – When should surgeons recommend? Joint Hospital Surgical Grand Round Dr Lorraine Chow Ruttonjee Hospital

Background Systemic therapy given before or after radical surgery may reduce recurrence in high risk patients It is a common practice for surgeons to refer patients with cancer for adjuvant chemotherapy

Introduction However, systemic chemotherapy is associated with various side effects

Introduction Should we submit all patients with cancer to adjuvant chemotherapy?

Specific side effects Colon cancer (5-FU, Oxaliplatin, Leucovorin) – Mainly systemic symptoms e.g. fatigue, neutropenia Breast cancer – Anthracyclines: cardiotoxicities, highly emetic; complete alopecia – Taxanes: peripheral neuropathies, infusion- related allergic reactions, neutropenia, asthenia, myalgia and oncholysis – Carboplatin: nephrotoxicity, thrombocytopenia and otological toxicity

Methods Using ‘Adjuvant! Online’ to evaluate the benefit of adjuvant chemotherapy by application of common clinical scenarios

Adjuvant! Online

Adjuvant!online

Review guidelines (Adjuvant! Version 8.0) NCCN 2006 NCI/ PDQ 2005 NCI November 2000 Concensus St Gallen Concensus 2005 ASCO 2004: aromatase inhibitors

Relapse rate of colon cancer %

Breast cancer

Second Generation Chemotherapy Examples – 6 cycles of 5-fluorouracil (5FU), epirubicin (Ellence, E), and cyclophosphamide (Cytoxan, C). For strong dose epirubicin programs – CA x 4 then Taxotere x 4

Third Generation Chemotherapy Examples – TAC * 6 – FEC *3 then D*3 – CA*4 then T*4 (all q2w) – FEC*4 then T*8 q1w These regimens in randomized trials have been shown to be superior (by ~20%) to Second Generation regimens.

Scenarios – reduction in relapse rate

F/60, minor health problems Grade I, ER +ve, tumour 1.1-2cm, node -ve

F/60, minor health problems, Grade I, ER +ve, tumor size cm, node -ve ↓6.5% ↓8.8% ↓15%

F/60, minor health problems, Grade I, ER +ve, tumor size >5.0cm, node -ve

F/60, minor health problems, Grade II, ER +ve, tumor size cm, node -ve

F/60, minor health problems, Grade III, ER +ve, T1a, node -ve

F/60, minor health problems, Grade III, ER +ve, tumor size cm

F/40, good past health Grade I, ER +ve, tumour cm, node -ve

F/40, good past health Grade I, ER +ve, tumour 1.1-2cm, node -ve

F/40, good past health Grade II, ER +ve, tumour 1.1-2cm, node -ve

F/40, good past health Grade III, ER +ve, tumour 1.1-2cm, node -ve

F/40, good past health Grade III, ER +ve, T1a, node -ve

F/40, Major health problems Grade III, ER +ve, T1a, node -ve

F/40, Minor health problems Grade I, ER +ve, T1a, node +ve

Scenarios – reduction in mortality rates

F/60, Minor health problems Grade III, ER +ve, T1a, node -ve

F/40, Minor health problems Grade I, ER +ve, T1a, node +ve

Conclusion Adjuvant therapy has little role in post- menopausal women with T1 and low grade tumours when Tamoxifen offers similar reduction rate However it significantly reduces relapse rate in younger, pre-menopausal patients with higher grade tumours, even if the size of tumour is small

Conclusion Nodal status is the most important predictive factor for relapse and adjuvant therapy is often recommended for node positive patients unless patient is unfit Benefits of adjuvant therapy is also affected by the general health of the patient

Thank you!

Adjuvant! Online The backbone of the efficacy estimates used in Adjuvant! are the Overview meta-analyses of randomized adjuvant chemotherapy and adjuvanthormone therapy trials for breast cancer (as last published in 1998), supplemented information presented as part of the 2000 Overview (although the formal analysis is still awaited(!)), and with Phase III clinical trial information.

Patient Characteristics 1. Unilateral, unicentric, invasive adenocarcinoma. 2. Prior definitive primary breast surgery and axillary node staging. 3. Not undergone pre-operative systemic therapy (usually referred to as neoadjuvant) or radiation therapy. 4. No evidence of metastatic or known residual disease. 5. No evidence of T4 features (extension to skin or chest wall). 6. No evidence of inflammatory breast cancer. 7. Plans to complete radiation therapy if the patient has had a lumpectomy.