A phase II trial to assess the activity of gemcitabine and docetaxel as first line chemotherapy treatment in patients with unresectable leiomyosarcoma

Patient characteristics

Between August 2004 and December 2007, 45 patients were enrolled from two sarcoma
units in London, UK. One patient was excluded from the analysis as she only received
one cycle of chemotherapy and so was considered non-evaluable for response (this patient
deteriorated rapidly after cycle 1 and died). No patients had received prior adjuvant
chemotherapy. Patient and disease characteristics are summarised in Table 1.

Table 1. Patient characteristics (n = 44)

Treatment and toxicity

The median number of cycles of study treatment per patient was 6 (range 2–8 cycles).
Eleven patients (25.0%) received 2 cycles, 4 (9.1%) received 3 cycles, 4 (9.1%) received
4 cycles, 2 (4.5%) received 5 cycles, 13 (29.5%) received 6 cycles, 1 (2.3%) received
7 cycles, and 9 (20.5%) received 8 cycles. Nine patients required a dose reduction
(25% in 8 patients, 50% in 1 patient). Of these, 8 patients started at 100% dose,
and 1 patient at 75% dose due to previous pelvic radiotherapy.

Toxicities observed with the study treatment are summarised in Table 2. The commonest toxicities (any grade) were anaemia (95%), fatigue (93%), alopecia
(88%), and thrombocytopenia (71%). The commonest grade 3 or 4 toxicities were fatigue
(30%), anaemia (24%), dyspnoea (16%), neutropenia (12%), and infection (any, 12%).
Eight patients (18%) stopped study treatment early specifically due to toxicity.

Table 2. Adverse events related to the study treatment

Treatment response and survival

RECIST-measured objective PR were observed in 11 patients (25%), and 16 patients (36.4%)
achieved confirmed SD. A further 7 patients (15.9%) had SD that was unconfirmed by
RECIST, and 10 patients (22.7%) had disease progression. Comparing uterine versus
non-uterine primary site, PR were seen in 8 (33%) and 3 (15%) patients, respectively,
and confirmed SD in 7 patients (29.3%) and 8 (40%) patients, respectively.

At a median follow-up of 41 months, the median PFS was 7.1 months (95% confidence
interval, CI, 5.7–8.3 months) (Figure 1), with progression-free rates at 3 and 6 months of 70.5% (95% CI 56.7–84.2%) and
59.1% (95% CI 44.3–73.9%), respectively. The median OS was 17.9 months (95% CI 10.6–25.2 months),
with OS rates at 12 and 24 months of 65.5% (95% CI 51.1–79.9%) and 33.6% (95% CI 18.8–48.4%),
respectively.

Figure 1. Kaplan–Meier curve of progression-free survival (days) for patients with advanced
leiomyosarcoma (n = 44). Median progression free survival 7.1 months (95% CI 5.7–8.3 months).

Post-progression treatment

After treatment within the study, further treatment was as follows: 31 patients received
second line systemic therapy (doxorubicin n = 31, ifosfamide n = 1, letrozole n = 1,
pazopanib n = 1), 12 patients received third line systemic therapy (clinical trial
n = 3, trabectedin n = 5, megesterol acetate n = 1, ifosfamide n = 2, gemcitabine
and docetaxel n = 1), and 1 patient received fourth line systemic therapy (ifosfamide).
Two patients underwent surgery (1 patient underwent palliative resection of residual
pelvic disease, 1 patient underwent resection of a uterine mass that was deemed inoperable
prior to chemotherapy), 2 patients received palliative radiotherapy alone, 6 patients
had no further treatment, and information was missing for 2 patients.