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Recommendations for use of Chemotherapy

Statements of evidence

The following statements of evidence support the NBOCC* recommendations for use of
chemotherapy for the treatment of advanced breast cancer.

STATEMENTS LEVEL OF EVIDENCE9 REFERENCE
In women with advanced breast cancer:
Combination chemotherapy increases response rates, time to progression, toxicity and overall survival, compared with single-agent chemotherapy, not including sequential use of the
same drugs
I Cochrane5
Combination chemotherapy increases response rates and toxicity, but not time to progression or overall survival, compared with sequential use of the same drugs as single agents II Sledge10
Soto11

In women with hormone receptor-positive disease:

  • initial chemotherapy achieves similar overall survival to initial endocrine therapy, except in those with visceral disease that is extensive or rapidly progressing, where initial chemotherapy shows improved survival
  • endocrine therapy has fewer adverse effects
    than chemotherapy
I Cochrane5
Dose
Higher-than-standard doses of chemotherapy increase tumour response and toxicity, but not time to progression or overall survival, compared with standard doses I Cochrane5
Lower-than-standard doses of chemotherapy do not improve quality of life and survival, compared with standard doses II Tannock37
Duration
Extending chemotherapy beyond the standard duration
(18–24 weeks; 6-8 cycles) delays progression but has limited effect on overall survival
I Gennari12
Shorter-than-standard durations (less than 18-24 weeks) of chemotherapy result in reduced overall survival and
quality of life
II Coates36
Taxanes

Single-agent taxanes give similar response rates and overall survival, but shorter time to progression compared with anthracyclines

Taxane-based combination chemotherapy increases response rates and time to progression, but not overall survival, compared with anthracyclines

I


II

Piccart-
Gebhart13

Sledge10

Paclitaxel

When compared with 3-weekly paclitaxel, use of
weekly paclitaxel:

  • increases time to progression and overall survival
  • causes less myelosuppression, but more neuropathy
  • requires more clinic visits
II CALGB 984014

For 3-weekly paclitaxel:

  • increasing the dose beyond 175mg/m2 increases toxicity, but not response rate, survival or quality of life
II CALGB 934215
Docetaxel

For 3-weekly docetaxel:

  • increasing the dose from 75 mg/m2 to 100 mg/m2 increases response rates and toxicity, but not time to progression or overall survival
  • reducing the dose from 75 mg/m2 to 60 mg/m2
  • decreases toxicity
II Harvey16
Docetaxel versus paclitaxel

3-weekly docetaxel and weekly paclitaxel both increase response rates, time to progression and overall survival, when compared with 3-weekly paclitaxel

No randomised trials in advanced breast cancer have directly compared 3-weekly docetaxel with weekly paclitaxel

II Jones34
CALGB 984014

When compared with paclitaxel, docetaxel causes:

  • more myelosuppression and gastro-intestinal toxicity
  • less neuropathy and allergic reactions
II Jones34
Albumin-bound paclitaxel  

When compared with standard 3-weekly paclitaxel, nanoparticle albumin-bound paclitaxel:

  • increases response rate and time to progression, but not overall survival
  • causes more neuropathy, fatigue and gastrointestinal toxicity, but less neutropenia and allergic reactions

Nanoparticle albumin-bound paclitaxel has not been compared with standard paclitaxel given weekly



II

II



Gradishar17

Guan18

Antimetabolites
Capecitabine as first-line chemotherapy for metastatic breast cancer
For women for whom more intensive chemotherapy is not appropriate, capecitabine improves overall survival and is better tolerated than oral cyclophosphamide, methotrexate and fluorouracil 5FU (CMF) II Stockler20
Antimetabolites and taxanes  
Capecitabine and docetaxel  

In women previously treated with an anthracycline, the combination of capecitabine and docetaxel, compared with single-agent 3-weekly docetaxel:

  • increases response rates, time to progression and overall surviva
  • increases toxicity
II O’Shaughnessy21
Gemcitabine and paclitaxel    

In women previously treated with an anthracycline, the combination of gemcitabine and paclitaxel, compared
with single-agent 3-weekly paclitaxel:

  • increases response rate, time to progression and overall survival
  • increases toxicity
II Albain22
Targeted therapies  
Trastuzumab
For women with HER2-positive advanced breast cancer, see NBCC’s* guideline Recommendations for use of trastuzumab (Herceptin®) for the treatment of HER2-positive breast cancer3
Bevacizumab with first-line chemotherapy for metastatic breast cancer

When compared with weekly paclitaxel alone, the addition
of bevacizumab:

  • improves response rates and time to progression, but not overall survival
  • causes more hypertension and proteinuria
II ECOG E210023, 39, 40

When compared with 3-weekly docetaxel alone, the addition
of bevacizumab:

  • improves response rates and time to progression, but not overall survival
  • causes more febrile neutropenia
II AVADO24
Bevacizumab with second- or third-line chemotherapy for metastatic breast cancer

In women previously treated with an anthracycline and taxane, the addition of bevacizumab to capecitabine, compared with capecitabine alone:

  • improves response rates, but not time to progression or overall survival
  • causes more hypertension, proteinuria and hand-foot syndrome
II Miller25
Lapatinib after progression on trastuzumab

When  compared with capecitabine alone, the addition of lapatinib after progression on trastuzumab:

  • improves response rates and time to progression, but not overall survival
  • causes more diarrhoea, dyspepsia, liver dysfunction
    and rash
II Geyer26, 27

* In February 2008, National Breast Cancer Centre (NBCC), incorporating the Ovarian Cancer Program, changed its name to National Breast and Ovarian Cancer Centre (NBOCC). In July 2011, NBOCC amalgamated with Cancer Australia to form a single national agency, Cancer Australia, to provide leadership in cancer control and improve outcomes for Australians affected by cancer.

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