SECOND LINE CHEMOTHERAPY FOR BREAST CANCER

THE GOALS
To maximise length of life (overall survival) and quality of life.

CHEMOTHERAPY DRUGS USED TO TREAT

ADVANCED BREAST CANCER alkylating agents, e.g. cyclophosphamide anthracyclines, e.g. doxorubicin, epirubicin antimetabolites, e.g. capecitabine, 5-fluorouracil, gemcitabine, methotrexate taxanes, e.g. docetaxel, paclitaxel, nab-paclitaxel vinorelbine.

THE SELECTION OF SPECIFIC CHEMOTHERAPY DRUGS, COMBINATIONS, DOSES, SCHEDULES AND DURATIONS IS BASED ON:
the pathological characteristics of the tumour, especially whether it expresses higher-than normal levels of the HER2 protein (HER2-positive tumours) the clinical characteristics of the tumour, especially its extent and growth rate

the womans past exposure and response to chemotherapy co-morbidities quality of life considerations including unwanted effects of chemotherapy the womans preferences the womans age practical considerations

DURATION OF CHEMOTHERAPY
Tumour response should be assessed every 612 weeks (23 cycles) during chemotherapy If disease control (stable disease or better) is confirmed and toxicity is tolerable, then chemotherapy should be continued for 1824 weeks (68 cycles) Extending chemotherapy beyond the standard duration (1824 weeks; 68 cycles) is an option if toxicity is minimal and the goal is to delay progression

ADVANCES IN TREATMENT
1980 1985 1990 1995 2000 2005
Tamoxifen CMF Doxorubicin Mitoxantrone Epirubicin Paclitaxel Vinorelbine Aromatase Inhibitors

ER+ or PR+ HER2+

Docetaxel Gemcitabine Capecitabine Fulvestrant Trastuzumab Albumin-Bound Paclitaxel Bevacizumab Lapatinib Ixabepilone

GEMCITABINE

GEMCITABINE PHARMACOLOGY

Difluorodeoxycytidine (dFdCyd) Belongs to group of antimetabolites (specific)

Undergoes intracellular metabolism

Blood, liver, and kidneys

Half-life of 8-17 min

GEM. PHARMACOLOGY CONTINUED

Analogue of deoxycytidine nuceloside Cell cycle specific

G0, G1, S, G2, and M Phase

Nucleoside Transporters

GEMCITABINE MECHANISM

GEMCITABINE APPLICATION

Chemotherapeutic Agent Treat various types of cancer

Non Small Cell Lung Cancer* Pancreatic Cancer Metastatic Breast Cancer* Ovarian cancer*

*Combination Therapy

Non Small Cell Lung Cancer Pancreatic Cancer Metastic Breast Cancer

Ovarian Cancer

CHEMOTHERAPY REGIMENS FOR MBC

2007 NCCN RECOMMENDATIONS
Representative Single Agents

Combination Regimens

Doxorubicin Epirubicin Pegylated liposomal doxorubicin Paclitaxel Docetaxel Capecitabine Vinorelbine Gemcitabine Albumin-bound paclitaxel

CAF/FAC (cyclophosphamide/doxorubicin/ fluorouracil) FEC (fluorouracil/epirubicin/cyclophosphamide) AC (doxorubicin/cyclophosphamide) EC (epirubicin/cyclophosphamide) AT (doxorubicin/docetaxel; doxorubicin/paclitaxel)

CMF (cyclophosphamide/methotrexate/fluorouracil)

Docetaxel/capecitabine GT (gemcitabine/paclitaxel)

F = fluorouracil; A = doxorubicin; C = cyclophosphamide; E = epirubicin; T = paclitaxel; M = methotrexate. National Comprehensive Cancer Network. Breast Cancer. Clinical Practice Guidelines in Oncology v.2.2007.

Gemcitabine is administered by the intravenous route Dose ranges from 1-1.2 g/m2 of body surface area according to type of cancer treated.

SIDE EFFECTS

Flu-like symptoms such as muscle pain, fever, headache, chills, and fatigue Fever (within 612 hours of first dose) Fatigue Nausea (mild) Vomiting Poor appetite Skin rash Allergic reaction Diarrhea Weakness Hair loss Mouth sores Difficulty sleeping Shortness of breath

CAPECITABINE

Capecitabine (Xeloda) 150 mg is an orallyadministered chemotherapeutic agent The pills are usually given for 14 days, then no pills for 7 days. Twice a day (morning and evening). This cycle is repeated every 3 weeks if you have no serious problems. Capecitabine prodrug, that is enzymatically converted to 5-fluorouracil in the body Breast Cancer as monotherapy/combotherapy; this is licensed as a second-line treatment in the UK)

INDICATIONS
breast cancer that has spread to other parts of the body (metastatic breast cancer). together with another medicine called docetaxel breast cancer that has spread to other parts of the body and has not improved after treatment with other medicines such as paclitaxel and anthracycline-containing medicine such as Adriamycin and doxorubicin.

MECHANISM OF ACTION

CONTRAINDICATIONS
History of hypersensitivity to fluorouacil, capecitabine or any of its excipients. Patients with DPD deficiency Pregnancy and lactation Patients with pre-existing blood dyscrasias Patients with severe hepatic impairment or severe renal impairment Treatment with sorivudine or its chemically related analogues, such as brivudine

USE WITH CAUTION IN

People over 60 years of age. Decreased kidney function. Decreased liver function. People with disease affecting the brain or nervous system. People with a history of heart disease such as angina or irregular heartbeats (arrhythmias). People with disturbances in the levels of electrolytes (in particular calcium) in their blood. Diabetes mellitus People with diarrhoea.

ADVERSE EFFECTS BY FREQUENCY:

Appetite loss Diarrhoea Vomiting Nausea Stomatitis Abdominal pain Fatigue Weakness Hand-foot syndrome Oedema Fever Headache Hair loss Dermatitis Shortness of breath Eye irritation Myelosuppression

THANK YOU