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AIMS: After failure of anthracycline- and taxane-based chemotherapy in metastatic breast cancer, treatment options until recently were limited. Until the introduction of capecitabine and vinorelbine, no standard regimen was available. We conducted a retrospective study to determine the efficacy and toxicity of platinum-based chemotherapy in metastatic breast cancer. MATERIALS AND METHODS: Forty-two women with metastatic breast cancer previously treated with anthracyclines (93%) and/or taxanes (36%) received mitomycin-vinblastine-cisplatin (MVP) (n=23), or cisplatin-etoposide (PE) (n=19), as first-, second- and third-line treatment at a tertiary referral centre between 1997 and 2002. Chemotherapy was given every 3 weeks as follows: mitomycin-C (8 mg/m2) (cycles 1, 2, 4, 6), vinblastine (6 mg/m2), and cisplatin (50 mg/m2) all on day 1; and cisplatin (75 mg/m2) and etoposide (100 mg/m ) on day 1 and (100 mg/m2) orally twice a day on days 2-3. RESULTS: The response rate for 40 evaluable patients (MVP: n=23; PE: n=17) was 18% (95% confidence interval [CI]: 9-32%). The response rate to MVP was 13% (95% CI: 5-32%, one complete and two partial responses) and to PE 24% (10-47%, four partial responses). Disease stabilised in 43% (26-63%) and 47% (26-69%) of women treated with MVP and PE, respectively. After a median follow-up of 18 months, 37 women (MVP: n=19; PE: n=18) died from their disease. Median (range) progression-free survival and overall survival were 6 months (0.4-18.7) and 9.9 months (1.3-40.8), respectively. Median progression-free survival for the MVP and PE groups was 5.5 and 6.2 months (Log-rank, P = 0.82), and median overall survival was 10.2 and 9.4 months (Log-rank, P = 0.46), respectively. The main toxicity was myelosuppression. Grades 3-4 neutropenia was more common in women treated with PE than in women treated with MVP (74% vs 30%; P = 0.012), but the incidence of neutropenic sepsis, relative to the number of chemotherapy cycles, was low (7% overall). The toxicity-related hospitalisation rate was 1.2 admissions per six cycles of chemotherapy. No treatment-related deaths occurred. MVP and PE chemotherapy have modest activity and are safe in women with metastatic breast cancer.

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OBJECTIVE: To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial. METHODS: Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 > or = 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m(2)) was given on day 1, and 5-Fluorouracil (370 mg/m(2)) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle. RESULTS: Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months. CONCLUSION: Oxaliplatin and 5-Fluorouracil/Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer.

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Cisplatin and carboplatin are active in previously untreated patients with metastatic breast cancer (MBC) with mean response rates (RRs) of 50 and 32%, respectively. In pretreated patients the RR to cisplatin/carboplatin monotherapy declines markedly to <10%. Cisplatin and carboplatin have been combined with many other cytotoxics. In first-line setting high activity has been observed in combination with taxanes or vinorelbine (RRs consistently approximately 60%). It appears that these newer combinations are superior to older regimens with etoposide (RRs 30 to 50%) or 5-fluorouracil (RRs 40 to 60%). Cisplatin-/carboplatin-based regimens with infusional 5-FU and epirubicin/paclitaxel/vinorelbine achieve high RRs of around 60 to 80%. However these regimens are difficult to administer in all patients because they require central venous access for continuous 5-FU infusion. In pretreated MBC the combinations of cisplatin-taxane/vinorelbine/gemcitabine or carboplatin-docetaxel/vinorelbine yield RRs of 40 to 50%, which are higher than those achieved with platinum-etoposide/5-FU. In locally advanced disease cisplatin-based regimens achieve very high RRs (>80%). This would suggest that in chemotherapy-naïve patients platinum-based therapy might have an important role to play. Additionally the synergy demonstrated between platinum compounds, taxanes and herceptin, in preclinical and clinical studies is of immense importance and the results of the two ongoing Breast Cancer International Research Group randomized phase III studies are eagerly awaited. These studies may help clarify the role of platinum compounds in the treatment of metastatic and possibly early breast cancer.

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BACKGROUND: The prognosis of patients with high-risk germ-cell cancer is poor. The toxicity and efficacy of first-line high-dose chemotherapy (HDCT) with stem-cell support was evaluated, following induction chemotherapy with BEP. PATIENTS AND METHODS: Twenty patients with poor prognosis non seminomatous germ-cell tumour by the International Consensus prognostic criteria received induction with BEP followed by one cycle of HDCT (CEC) given with carboplatin (1800 mg/m2), etoposide (1800 mg/m2), and cyclophosphamide (140 mg/kg). Of the above 20 patients only 3 received a second cycle of HDCT. Peripheral blood stem cells were infused on day 0. RESULTS: Twenty patients were assessable for toxicity and response. After a median follow-up of 27 months 15 patients (75%) are alive, 12 (60%) are disease free and 3 (15%) are alive with disease. Median survival has not been reached and overall survival at four years is 66% with a durable complete response rate of 50%. There were no deaths or cases of severe toxicity. Median time to a granulocyte count > 500/microl and platelets > 20,000/microl was 10 and 12 days respectively. Five patients have died from progressive disease 5-35 months after HDCT. CONCLUSIONS: These results support the case of first-line HDCT. The excellent toxicity profile of BEP/CEC and the two-year overall survival of 78% are encouraging and support further the ongoing randomised US intergroup study evaluating high-dose CEC after BEP.

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