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Pajk et al. (2008)

Pajk et al. (2008)
Design: Randomised phase II study (therapy). Evidence level 3
Country: Slovenia
Inclusion criteria:
Women with metastatic breast cancer
Measurable disease
Previous treatment with anthracycline and taxane (adjuvant or metastatic setting) unless CI
Age > 18 years
KPS ≥ 70%
Written informed consent
Exclusion criteria:
Significant cardiac disease
CNS metastases
Sensitivity to fluoropyrimidines
Neurotoxicity ≥ grade 2
Previous treatment with 5′-FU, vinca alkaloids or > 2 chemotherapy lines
Number of patients = 47. Age range: 31 to 71 years. Median age 50/54 years
  1. Vinorelbine (VIN) at 30 mg per m2 i.v. on days 1 and 8 every three weeks
  2. Oral capecitabine (CAP) at 1250 mg per m2 twice a day every 14 days in every three weeks.
In those women with a response or stable disease, chemotherapy was given until disease progression, unacceptable toxicity or patient refusal. Drug modifications were made for particular (not specified) haematological and other toxicities.
Primary outcome: Tumour response: complete response (CR), partial response (PR), Overall response (OR = CR + PR), stable disease (SD), disease progression (PD)
Secondary outcomes: response duration (RD), clinical benefit ratio (OR + SD ≥ 24 weeks), time to progression, (TTP), safety.
Follow up:
Response evaluation was performed one week before randomisation and then every 6 weeks during chemotherapy until disease progression. All patients were eligible to be included in both the efficacy and toxicity analyses.

14 women (6 in CAP and 8 in VIN arms) could not be assessed for tumour response either because of withdrawal due to toxicity or non-compliance with follow-up – these participants were classified as non-assessable.
Survival was estimated after a median follow-up of 17 months.
Efficacy CAP arm (n=23):
CR = 1
PR = 1
OR = 2 (8.6%)
SD = 5
CBR = 7 (34%)
PD = 10
Not assessable = 6

Efficacy VIN arm (n=24):
CR = 0
PR = 3
OR = 3 (12.5)
SD = 5
CBR = 8 (33%)
PD =8
Not assessable = 8

Median RD of CAP responders = 4.4 months (range: 1.4–7.5)
Median RD of VIN responders = 4.2 months (range: 2.6–5.1)

Median PFS for CAP = 2.8 months (95%CI: 1.8–6.3)
Median PFS for VIN = 2.6 months (95%CI: 1.7–4.7)

Median OS for CAP = 9.3 months (7.5-not reached)
Median OS for VIN = 11.0 months (8.1–14.6)

Grade 3/4 adverse events in CAP arm (n=23) %:
Nausea = 4
Vomiting = 4
Hand-foot syndrome = 4
Fatigue = 4
Infection = 4
Neutropenia = 4

Grade 3/4 adverse events in VIN arm (n=24) %:
Constipation = 4
Abdominal pain = 13
Fatigue = 13
Infection = 8
Neutropenia = 46
Febrile neutropenia = 13
General comments:
This paper reports the findings from a multi-national study which was designed to compare CAP with VIN as therapy after prior anthracycline and taxane for advanced disease. The planned participant size was 72 and hence, having only enrolled women 47 before accrual closed, this study was very underpowered to detect differences between the two treatment groups and, presumably for this reason, no comparative statistics were reported. Nevertheless, the two groups were randomised (no details given) and were well balanced in most respects. More women in the VIN arm had taxane sensitivity and more women in the CAP arm had visceral disease.

The treatment protocol was violated in 42.5% of patients, mainly by not following the specific dose reduction (11 in CAP arm and 6 in VIN arm).

The authors concluded that, although this was not a meaningful direct comparison, both agents appeared to have equal efficacy for heavily pre-treated patients with metastatic breast cancer although vinorelbine appeared to have more adverse events (although which are non- overlapping between therapies). Apparently the trial was unable to accrue planned numbers due to patient and physician preference of the (then) recent availability of oral CAP.

From: Chapter 4, Systemic disease-modifying therapy

Cover of Advanced Breast Cancer
Advanced Breast Cancer: Diagnosis and Treatment.
NICE Clinical Guidelines, No. 81.
National Collaborating Centre for Cancer (UK).
Copyright © 2009, National Collaborating Centre for Cancer.

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