1. PHASE I/II STUDY OF PEGYLATED LIPOSOMAL DOXORUCIN (PLD) AND GEMCITABINE (GEM) IN RECURRENT PLATIN RESISTANT OVARIAN CANCER (OC).
A Study of the VWOG

2. Caelyx and Gemcitabine in recurrent ovarian cancer
Rationale
Pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) are 2 active drugs in recurrent ovarian cancer.
Few trials have investigated the combination of these 2 drugs in this setting.
Despite the fact that PLD is usually given in a 4-week schedule, most Phase II studies in ovarian and breast cancer have used a 3-week regimen with this combination.
Given encouraging response rates on other diseases and the lower incidence of PPE and bone marrow toxicity with a 4 weeks schedule of PLD, the present study is testing the combination of PLD and GEM in a 4-week schedule.

3. Caelyx and Gemcitabine in recurrent ovarian cancer
PHASE I (n=17)
Cohort N
Caelyx q 4 weeks
Gemcitabine d1, q 4 weeks 1a 3
30 mg/m2
1000 mg/m2 1b
35 mg/m2 1c
40 mg/m2 1d
50 mg/m2 n
Gemcitabine d1,8, q 4 weeks 2a
650 mg/m2 2b
800 mg/m2 2c 2d

4. Caelyx and Gemcitabine in recurrent ovarian cancer
PHASE I (n=17) (reported ESGO 2007)
First cohort 1a to 1d will be accrued up to MTD followed by 2a to 2d up to the MTD.
The dose limiting toxicity was Grade 4 trombocytopenia.
Dose level 2b was the recommended schedule:
PLD 30 mg/m² on day 1
GEM 800 mg/m² on day 1,8, 15 q 4 weeks.

5. Caelyx and Gemcitabine in recurrent ovarian cancer
PHASE II (n=24) Inclusion Criteria
Histological diagnosis of epithelial ovarian, fallopian tube or peritoneal carcinoma.
Measurable disease (RECIST)
Patient has received at least one or two prior platin-based chemotherapy regimens for advanced or metastatic disease, and a treatment-free interval of less than 6 months after the last platin- based chemotherapy.
No prior Anthracyclines or Gemcitabine therapy.
Second-line retreatment with (taxanes)/platin was allowed. Second- line therapy with other drugs was not allowed.
Left ventricular ejection fraction  50 % as determined by MUGA (isotopic methods) or ultrasound.

6. Caelyx and Gemcitabine in recurrent ovarian cancer
PHASE II (n=24)
In total 109 courses were administered
Toxicities
Number of patients / grade G3 G4
Haematologic 
Hemoglobin 9
Neutrophiles 12 4
Platelets 7 8
Gastrointestinal
stomatitis 1
nausea
vomiting
other toxicities
fatigue 2

7. Caelyx and Gemcitabine in recurrent ovarian cancer
Efficacy Phase II (n=20) N
Complete Reponse 2
Partial Response 4
Stable Disease (> 6 months) 8
Progression 6
Total Response
6 (30%)
Clinical benefit (Response or SD > 6 months)
17 (70%)

8. Caelyx and Gemcitabine in recurrent ovarian cancer
Efficacy Phase II (n=20)
Median (months)
Range (months)
Follow-up 16
5-28
Overall survival 12
4-28
Progression-free survival 11
1-16
Duration response 9
8-16

9. Caelyx and Gemcitabine in recurrent ovarian cancer
Conclusion
Caelyx and Gemzar in a 4 weekly regimen resulted in platin resistant recurrent ovarian cancer compared with other treatment options:
acceptable toxicity
interesting response rate (30%),
clinical benefit (70%) and PFS (9 monts). .