Adjuvant chemotherapy – When should surgeons recommend?

Joint Hospital Surgical Grand Round

Dr Lorraine ChowRuttonjee 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 problemsGrade I, ER +ve, tumour 1.1-2cm, node -ve

F/60, minor health problems, Grade I, ER +ve, tumor size 2.0-3.0cm, 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 1.1-2.0cm, 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 1.1-2.0cm

F/40, good past healthGrade I, ER +ve, tumour 0.1-1.0cm, node -ve

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

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

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

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

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

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

Scenarios – reduction in mortality rates

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

F/40, Minor health problemsGrade 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.