Table 2 ATRA in breast cancer clinical trials

ClinTR1

ATRA

Phase II

14

ATRA administered orally at a dose of 50 mg/mq three times a day for 14 consecutive days of a 21-day cycle

Metastatic breast cancer

1) Evaluation of tumor growth; 2) characterization of ATRA pharmacokinetics

1) no significant antitumor activity; 2) high degree of interpatient variability in plasma levels of ATRA

Sutton et al., Cancer Chemother Pharmacol,1997 [141]

ClinTR2

ATRA plus tamoxifen

Phase I/II

25

ATRA administered orally at a dose of 70, 110, 150, 190, or 230 mg/mq/day on odd-numbered weeks (consecutive cohorts of 3–6 patients). Tamoxifen administered at 20 mg daily

Hormone-responsive advanced breast cancer

1) Determination of the maximum tolerated dose; 2) evaluation of tumor progression; 3) characterization of ATRA pharmacokinetics

1) doses up to 190 mg/mq were tolerable; 2) objective responses were observed, some in patients who had previously progressed while receiving tamoxifen; 3) high degree of intra and interpatient variability in plasma ATRA concentration

Budd et al., Clinical Cancer Res, 1998 [142]

ClinTR3

ATRA plus paclitaxel

Phase II

17

ATRA administered orally at 45 mg/mq PO daily for 4 days starting 2 days before a 1 h treatment with paclitaxel (Taxol, Bristol-Myers Squibb, Plainsboro, NJ) 80 mg/mq IV administered weekly for 3 weeks, repeated in 28 day cycles until disease progression or until no longer tolerated

Recurrent or metastatic breast cancer

1) Evaluation of toxicity, response; 2) determination of time to progression and survival

1) ATRA is a well-tolerated regimen; 2) Time to progression and survival rates similar to those reported for paclitaxel alone

Bryan et al., Invest New Drugs, 2011 [143]

ClinTR4

ATRA plus anastrozole

Phase II

n.d.

ATRA administered orally at 45 mg/mq/day for 28 days. Anastrozole administered orally at 1 mg daily

Operable Estrogen Receptor positive/HER2-negative early breast cancer

Evaluation of ATRA biological effect on: 1) percentage of Ki67; 2) tumor size reduction; 3) response rate.

n.d.

n.d.