WAT). The investigator measured the percentage total body surface area (%TBSA) involvement separately for patches, plaques, and tumors within 12 body regions using the patient's palm as a "ruler". The total %TBSA for each lesion type was multiplied by a severity weighting factor (1=patch, 2=plaque and 4=tumor) and summed to derive the SWAT score. Efficacy was measured as either a Complete Clinical Response (CCR) defined as no evidence of disease, or Partial Response (PR) defined as a ≥50% decrease in SWAT skin assessment score compared to baseline. Both CCR and PR had to be maintained for at least 4 weeks.
Secondary efficacy endpoints included response duration, time to progression, and time to objective response.
The population had been exposed to a median of three prior therapies (range 1 to 12).
Table 2 summarizes the demographic and disease characteristics of the Study 1 population.
Table 2: Baseline Patient Characteristics (All Patients As Treated) Vorinostat
Characteristics (N=74)
Age (year)
Mean (SD) 61.2 (11.3)
Median (Range) 60.0 (39.0, 83.0)
Gender, n (%)
Male 38 (51.4%)
Female 36 (48.6%)
CTCL stage, n (%)
IB 11 (14.9%)
IIA 2 (2.7%)
IIB 19 (25.7%)
III 22 (29.7%)
IVA 16 (21.6%)
IVB 4 (5.4%)
Racial Origin, n (%)
Asian 1 (1.4%)
Black 11 (14.9%)
Other 1 (1.4%)
White 61 (82.4%)
Time from Initial CTCL Diagnosis (year)
Median (Range) 2.6 (0.0, 27.3)
Clinical Characteristics
Number of prior systemic treatments, median (range) 3.0 (1.0, 12.0)
The overall objective response rate was 29.7% (22/74, 95% CI [19.7 to 41.5%]) in all patients treated with ZOLINZA. In patients with Stage IIB and higher CTCL, the overall objective response rate was 29.5% (18/61). One patient with Stage IIB CTCL achieved a CCR. Median times to response were 55 and 56 days (range 28 to 171 days), respectively in the overall population and in patients with Stage IIB and higher CTCL. However, in rare cases it took up to 6 months for patients to achieve an objective response to ZOLINZA.
The median response duration was not reached since the majority of responses continued at the time of analysis, but was estimated to exceed 6 months for both the overall population and in patients with Stage IIB and higher CTCL. When end of response was defined as a 50% increase in SWAT score from the nadir, the estimated median response duration was 168 days and the median time to tumor progression was 202 days.
Using a 25% increase in SWAT score from the nadir as criterion for tumor progression, the estimated median time-to-progression was 148 days for the overall population and 169 days in the 61 patients with Stage IIB and higher CTCL.
Response to any previous systemic therapy does not appear to be predictive of response to ZOLINZA.
Study 2
In an open-label, non-randomized study, ZOLINZA was eva luated to determine the response rate for patients with CTCL who were refractory or intolerant to at least one treatment. In this study, 33 patients were assigned to one of 3 cohorts: Cohort 1, 400 mg once daily; Cohort 2, 300 mg twice daily 3 days/week; or Cohort 3, 300 mg twice daily for 14 days followed by a 7-day rest (induction). In Cohort
