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 woman’s past exposure and response to chemotherapy

co-morbidities quality of life considerations including

unwanted effects of chemotherapy the woman’s preferences the woman’s age practical considerations

DURATION OF CHEMOTHERAPY Tumour response should be assessed every

6–12 weeks (2–3 cycles) during chemotherapy

If disease control (stable disease or better) is confirmed and toxicity is tolerable, then chemotherapy should be continued for 18–24 weeks (6–8 cycles)

Extending chemotherapy beyond the standard duration (18–24 weeks; 6–8 cycles) is an option if toxicity is minimal and the goal is to delay progression

ADVANCES IN TREATMENT1980 1985 1990 1995 2000 2005

Capecitabine

Bevacizumab

Paclitaxel

CMF

Gemcitabine

Albumin-Bound Paclitaxel

Trastuzumab

Lapatinib

Doxorubicin

EpirubicinMitoxantrone

Vinorelbine

Docetaxel

HER2+

Aromatase Inhibitors

Tamoxifen

ER+ or PR+ Ixabepilone

Fulvestrant

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 TherapyNon Small Cell Lung CancerPancreatic CancerMetastic Breast CancerOvarian Cancer

Representative Single Agents

CHEMOTHERAPY REGIMENS FOR MBC2007 NCCN RECOMMENDATIONS

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.

Combination Regimens

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 6–12 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 orally-administered 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

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