Ulrich Stein

Intra-operative intra-peritoneal chemotherapy with cisplatin in patients with peritoneal carcinomatosis of ovarian cancer.

BackgroundIntra-peritoneal (i.p.) chemotherapy is an encouraging treatment option for ovarian cancer with peritoneum involvement in addition with intravenous (i.v.) chemotherapy. Intra-operative i.p. chemotherapy is an interesting method of administration by enhancing the diffusion of chemotherapy. This study had assessed the feasibility of intra-operative i.p. chemotherapy in patients with peritoneal carcinoma of ovarian cancer.MethodsFrom January 2003 to February 2006, 47 patients with stage III ovarian cancer were treated with standard paclitaxel carboplatin intravenous chemotherapy and debulking surgery with intra-operative i.p. chemotherapy. After optimal cytoreductive surgery, defined by no unresectable residual disease > 1 cm, i.p. chemotherapy was performed during surgery. The peritoneal cavity was filled by 3 litres of isotonic saline pre-heated at 37 degrees and 90 mg of cisplatin. The sequence was repeated twice during 2 hours based on previous published studies which optimized the cisplatin dosage and exposure duration. Optimal diffusion was obtained by stirring by hands during the 2 hours.ResultsMedian age was 59.6 years. No severe haematological or non-haematological toxicity induced by intra operative i.p. chemotherapy was reported. No patient died due to the complications of surgery or the i.p. chemotherapy. No neurotoxicity occurred, and one patients had renal impairment.ConclusionThis study demonstrates the feasibility of intra-operative i.p. chemotherapy with cisplatin after optimal resection of peritoneal tumor nodules. Further randomized trials are planned to investigate the clinical benefit of this therapeutic modality.

Ixabepilone, a novel epothilone analog in the treatment of breast cancer

Background: Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing cell death. Ixabepilone (BMS-247550, Ixempra®) is an epothilone analog that optimizes the properties naturally observed with epothilone B. Objective: To provide an overview of the results achieved by ixabepilone in metastatic breast cancer. Methods: A PubMed search was performed to provide an extensive review of all published data on ixabepilone, in addition to all data reported from international congresses, from 2003 to 2007. Results/conclusion: There is a clear need for new agents active against resistant metastatic breast cancer and ixabepilone might be a welcome new compound in this situation.

Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma

Introduction The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. Patients and methods All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. Results For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13–22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22–0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31–0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22–0.82], P=0.002). Median OS was 21 months [14–29 months] for patients who received at least one targeted therapy compared with 12 months [7–15 months] for patients who were treated only by immunotherapy agents (P=0.003). Conclusion Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications.

Economic impact of simplified de Gramont regimen in first-line therapy in metastatic colorectal cancer.

The cost of chemotherapy has dramatically increased in advanced colorectal cancer patients, and the schedule of fluorouracil administration appears to be a determining factor. This retrospective study compared direct medical costs related to two different de Gramont schedules (standard vs. simplified) given in first-line chemotherapy with oxaliplatin or irinotecan. This cost-minimization analysis was performed from the French Health System perspective. Consecutive unselected patients treated in first-line therapy by LV5FU2 de Gramont with oxaliplatin (Folfox regimen) or with irinotecan (Folfiri regimen) were enrolled. Hospital and outpatient resources related to chemotherapy and adverse events were collected from 1999 to 2004 in 87 patients. Overall cost was reduced in the simplified regimen. The major factor which explained cost saving was the lower need for admissions for chemotherapy. Amount of cost saving depended on the method for assessing hospital stay. In patients treated by the Folfox regimen the per diem and DRG methods found cost savings of €1,997 and €5,982 according to studied schedules; in patients treated by Folfiri regimen cost savings of €4,773 and €7,274 were observed, respectively. In addition, travel costs were also reduced by simplified regimens. The robustness of our results was showed by one-way sensitivity analyses. These findings demonstrate that the simplified de Gramont schedule reduces costs of current first-line chemotherapy in advanced colorectal cancer. Interestingly, our study showed several differences in costs between two costing approaches of hospital stay: average per diem and DRG costs. These results suggested that standard regimen may be considered a profitable strategy from the hospital perspective. The opposition between health system perspective and hospital perspective is worth examining and may affect daily practices. In conclusion, our study shows that the simplified de Gramont schedule in combination with oxaliplatin or irinotecan is an attractive option from the French Health System perspective. This safe and less costly regimen must compared to alternative options such as oral fluoropyrimidines.

A retrospective study of bifractionated CPT-11 with LF5FU infusion (FOLFIRI-3) in colorectal cancer patients pretreated with oxaliplatin and CPT-11 containing chemotherapies.

Objective:The chemotherapy regimen suitable for advanced colorectal cancer patients previously treated with 5 fluorouracil (5FU); oxaliplatin and irinotecan remains an unresolved issue. The poor response rates and progression-free survival achieved with FOLFIRI in the second-line of therapy and the schedule-dependent activity of irinotecan, prompted us to assess the efficacy and tolerability of FOLFIRI3 regimen in patients with metastatic colorectal cancer (CRC) previously exposed to irinotecan and oxaliplatin. Methods:Twenty-seven metastatic CRC patients previously exposed to irinotecan and/or oxaliplatin were treated with the FOLFIRI3 regimen. They received an irinotecan injection at 100 mg/m2 before and at the end of a 2400 mg/m2 5FU continuous infusion. Two hundred and six cycles of chemotherapy were delivered in an outpatient basis. Results:FOLFIRI3 regimen was well tolerated. Grade 3 of 4 adverse events included nausea and vomiting (18%), diarrhea (11%), anemia (7%), and neutropenia (7%). Partial responses were observed in 2 patients and 10 patients achieved stable diseases. From the start of FOLFIRI3, time to progression was 4.47 months (0–11 months) and median overall survival was 8.9 months (0.72–21.4 months). Interestingly, FOLFIRI3 treatment was associated to a clinical benefit in 7 out of 17 patients who previously progressed “on-therapy” or less than 3 months after the completion of a previous FOLFIRI chemotherapy. Conclusion:These results suggest that fractionated irinotecan administration might restore the clinical benefit of this molecule in patients resistant to FOLFIRI.

Carboplatin-etoposide combination chemotherapy in metastatic castration-resistant prostate cancer: A retrospective study

The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differentiated neuroendocrine cancers, such as small-cell lung cancer. The aim of this study was to assess the efficacy and tolerability of the carboplatin-etoposide regimen in metastatic castration-resistant prostate cancer (mCRPC). A total of 27 patients treated by carboplatin [area under the curve (AUC)=5] and etoposide (100 mg/m2 intravenous infusion on days 1–3 or 75 mg orally/day for 10 days) for mCRPC were included for analysis. The median progression-free survival was 3.3 months [95% confidence interval (CI): 1.9–4.2] and the median overall survival (OS) was 8.1 months (95% CI: 4.06–12.36). The main grade 3–4 toxicities were haematological, namely anemia (33.3%), neutropenia (25.9%) and thrombocytopenia (22.2%), whereas the most common non-hematological toxicity was asthenia (22.2%). The efficacy, compliance and safety profile were generally similar between the oral and intravenous etoposide groups. Pretreated patients with mCRPC may benefit from the carboplatin-etoposide regimen in terms of OS. The toxicities were acceptable, without reported treatment-related mortality. Therefore, the oral etoposide regimen may be an viable alternative for improving the quality of life of the patients. However, this regimen requires further prospective investigation to confirm its efficacy.

Anticancer therapy in patients with porphyrias: evidence today

Background: Porphyrias are rare diseases, and for these patients every administration of drugs may induce an acute attack of porphyria. The list of safe compounds allowed in these patients is available for clinicians from specific websites cited in the text. Objectives: However, data concerning anticancer therapy in patients with such diseases remain poor. Therefore any publications can help clinicians to deal with this very specific group of patients. Methods: In our institution, three patients received docetaxel and hematologic growth factors (erythropoietin and GCSF) without unexpected toxicities. Aromatase inhibitors (anstrozole and letrozole) were also given in one patient without any related problem. Conclusion: The present observation adds some useful data for the possible treatment of cancer in patients with porphyria.