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Introduction:Current therapies for recurrent ovarian cancer (OC) yield relatively modest improvements in survival. Many drugs are available but recently a renewed interest is addressed on antimetabolite drugs. Pemetrexed (PEM) is a multitargeted antifolate cytotoxic agent mainly used in lung cancer.Areas covered:This review summarizes the available evidence on the use of PEM in the treatment of OC. This article consists of material obtained via Medline, PubMed and EMBASE literature searches, up to November 2011. Currently available published data on mechanism of action, pharmacokinetics, safety and efficacy of PEM in the treatment of recurrent OC are described.Expert opinion:Eight trials evaluated the use of PEM in OC patients. Studies using PEM in combination with carboplatin in platinum-sensitive OC suggested that the response rate is similar to other combination therapies. However, based on the absence of randomized trials comparing this doublet with currently used combination treatments, it is difficult to draw conclusions on the efficacy of PEM regimens in these patients. In platinum-resistant OC patients, two studies suggested that PEM alone might have equivalent activity to other single-agent treatment. Further pharmacogenomic and clinical data are warranted to better define the role of PEM in the treatment of recurrent OC.

From June 1990 to October 1994, 111 advanced ovarian cancer patients with minimal (less than 2 cm) residual disease after platinum-based front-line chemotherapy and second-look laparotomy entered a cooperative randomized study aimed at evaluating the effectiveness and the toxicity of the addition of interferon-α2 to carboplatin, both intraperitoneally (ip) administered. Patients were randomized to receive either 3 courses of ip Carboplatin 400 mg/m2Day 1 q 28 days (54 pts) (CBDCA) or ip interferon-α 25 × 106U Day 1 + ip carboplatin 400 mg/m2Day 2 q 28 days (57 pts) (CBDCA + IFN). Patients treated with interferon experienced more severe (WHO grade 3–4) leukopenia (28% vs 17.1%) and anemia (14% vs 4.2%). Fever (P= 0.000) and flu-like syndrome (P= 0.02) were significantly more frequent in the combination arm. No difference in gastroenteric, neurologic, or renal toxicity was observed. At a median follow-up time of 13 months (range 1–72) 71 patients showed a disease progression (31 CBDCA, 40 CBDCA + IFN) and 44 patients died (21 CBDCA, 23 CBDCA + IFN). Median progression-free survival was 11 months in the CBDCA group and 10 months in the CBDCA + IFN arm. Median survival was 22 and 29 months in CBDCA and CBDCA + IFN arm, respectively. In conclusion, intraperitoneal interferon-α does not seem to improve the results achievable with intraperitoneal carboplatin in this subset of patients, while the toxicity and the costs of the combination are consistently higher than with chemotherapy alone.

40 N≥10 b.c. pts (median age: 46 yrs, range 31–56; median number of involved nodes: 13, range 10–33) were entered so far into a pilot trial to evaluate the feasibility of an adjuvant H.D. CT program without the use of stem cell support. Pts were given 3 cycles of CYC 600mg/m2d. 1, EPIDOX 60mg/m2d. 1, 5-FU 600mg/m2d. 1, q. 3 wks, followed by H.D. CT, administered in protect environment as needed, with CYC 2500 mg/m2dd. 1,2; VP 16 500mg/m2dd. 1–3; CDDP 50mg/m2dd. 1–3. Granulocyte-colony stimulating factor (G-CSF) was administered in all patients beginning on day 5 from H.D. CT and continued until leukocyte count reached 10 × 109/L. Median duration of granulocytopenia <500/μl was 7 days (5–10) and that of thrombocytopenia <20.000/μ1 was 3 days (1–5). The recovery to an ANC of at least 500/μ1 took a median of 15 days (13–17). No toxic death occurred. Median red cell transfusion requirement was 2 unit (0–4), and median platelet unit requirement was 1 unit (1–4). At a median follow up time of 14 mos (range 1–27), 5 pts are relapsed and 2 are dead. In conclusion, H.D. CT for high risk b.c. pts seems to be feasible and promising even without bone marrow rescue. Supported in part by ACRO, CNR contract No 94.01242.PF39.

Paclitaxel activity with or without ifosfamide was investigated as salvage therapy in patients (pts) with a.o.c. Group I (n = 20 evaluable) pts received taxol alone 175mg/m2, over 3 hours, every 3 weeks. Group II (n = 13 evaluable pts) received taxol 135mg/m2as in Group I; escalating doses of ifosfamide (1; 1.5; 2 gr/m2) was administered on days 2–3 with mesna rescue. In absence of severe toxicity, ifosfamide was administered at 2 gr/m2for the last three cycles. The average number of courses was respectively 4 in Group I (range 1–8) and 3 in Group II (range 1–6). Overall, 3 PR were observed in 15 pts with primary platinum resistant disease, 2 PR were observed in 8 pts with platinum sensitive disease while no response was observed in 10 pts with secondary platinum resistant ovarian cancer. Our results, although preliminary, suggest that taxol ± ifosfamide show a moderate but definite activity in so heavily pretreated category of pts. As expected the activity in platinum sensitive pts was twofold the activity achieved in platinum resistant pts, showing respectively 25% of PR vs 12% of PR. However, was to note that a 20% of activity was observed in primary platinum resistant pts. Moreover taxol plus ifosfamide association seems not to achieve better results than taxol alone, while it showed a higher haematologic toxicity. It is concluded that the number of previous therapeutic lines rather than the intrinsic sensitivity to cisplatin front line treatment is probably the major determinant of taxol activity when employed as salvage treatment.