Expected benefits of topotecan combined with lapatinib in recurrent ovarian cancer according to biological profile: a phase 2 trial.

OBJECTIVE: Lapatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), also inhibits breast cancer resistance protein (BCRP) involved in resistance to topotecan. The aim of this multicenter study was to assess the efficacy of the combination topotecan-lapatinib in epithelial ovarian cancer relapsing after a first line of chemotherapy. METHODS: Patients having relapsed within 6 months (n = 20) or between 6 and 12 months (n = 19) received weekly topotecan (3.2 mg/m given intravenously on days 1, 8, and 15) and daily oral lapatinib (1250 mg). Translational studies were performed on tumor and serum. RESULTS: An objective (partial) response was observed for 5 patients (14%), all with late relapse. The rates of overall benefits, including responses and stabilizations, were 37% and 62% in patients having relapsed within or after 6 months, respectively. Corresponding median time to progression were 58 and 94 days. The most frequent toxicity was hematological, including grade 4 neutropenia (18%) and thrombocytopenia (3%). None of the tumors overexpressed HER2 or EGFR, and no mutation was found. Two Kras mutations were identified. Positive expressions of BCRP and cyclin A (median, 70% and 40%) were not correlated to the response to treatment. CONCLUSIONS: This study failed to demonstrate a clinical benefit of lapatinib-topotecan compared to previously described activity with topotecan alone in a context of low levels of EGFR and HER2 expressions, and no biomarkers could be identified. The absence of correlation between BCRP expression and clinical outcomes suggests that other mechanisms of resistance to topotecan could predominate.

Diffusely increased F-18 FDG uptake in bone marrow in a patient with acute anemia and recent erythropoietin therapy.

Diffuse uptake of F-18 fluorodeoxyglucose (FDG) by the whole skeleton has been described in case of bone marrow stimulation resulting from treatment with colony-stimulating factors (CSFs): granulocyte CSF or granulocyte-macrophage CSF. The authors describe such an aspect of diffuse FDG uptake by the bone marrow during the follow-up of rectal cancer in a patient with anemia and recently treated thrice weekly by erythropoietin. To their knowledge, such an aspect of diffuse FDG uptake by the skeleton, revealing the bone marrow stimulation by erythropoietin, has not yet been reported.

Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma.

PURPOSE: Sunitinib and sorafenib are novel tyrosine kinase inhibitors (TKIs) that have shown significant clinical activity in metastatic clear cell renal cell carcinoma (RCC). The activity of sunitinib and sorafenib in non-clear cell histologies has not been evaluated. PATIENTS AND METHODS: Clinical features at study entry and treatment outcomes were evaluated in patients with metastatic papillary RCC (PRCC) and chromophobe RCC (ChRCC) who received either sunitinib or sorafenib as their initial TKI treatment in five US and French institutions. Response rate and survival were documented. Fisher's exact test was used for categoric variables, and the Kaplan-Meier method was used to estimate survival. RESULTS: Fifty-three patients were included. The number of patients with papillary and chromophobe histologies was 41 (77%) and 12 (23%), respectively. Response rate, progression-free survival (PFS) time, and overall survival time for the entire cohort were 10%, 8.6 months, and 19.6 months, respectively. Three (25%) of 12 ChRCC patients achieved a response (two patients treated with sorafenib and one treated with sunitinib), and PFS was 10.6 months. Two (4.8%) of 41 PRCC patients achieved a response (both patients were treated with sunitinib). PFS for the whole cohort was 7.6 months. Sunitinib-treated PRCC patients had a PFS of 11.9 months compared with 5.1 months for sorafenib-treated patients (P < .001). CONCLUSION: Patients with PRCC and ChRCC may have prolonged PFS from sunitinib and sorafenib, although clinical responses remain overall low in PRCC. Additional prospective trials with these agents in non-clear cell RCC will further clarify their use in the future.

[Locally advanced prostate cancer: definition, prognosis and treatment]. / Cancer de la prostate localisé à haut risque: définition, pronostic et traitement.

According to d'Amico's criteria, high-risk localized prostate cancer are defined either by an extracapsular extension (T3 or T4), either by a high Gleason score (> 7) or a PSA rate higher than 20 ng/ml. Pelvic lymph node involvement also corresponds to locally advanced prostate cancer. Statistical models called nomograms have been developed to predict the probability of prostate cancer recurrence and are also used to define locally advanced patients. Prostate MRI may help to detect an extracapsular extension or a seminal vesicles involvement but remains still discussed. A bone scan, an abdominal and pelvic CT scan have to be performed in order to detect metastases. A pelvic lymph node dissection is recommended in order to adapt the treatment of these patients. Standard treatment for high-risk localized prostate cancer without lymph node involvement is now well defined. The association of both local radiation and a long androgen deprivation (GnHR agonist) showed an overall survival benefit (more than 10%). The radiation dose of 74 Gy is recommended. Other questions are still debating : the optimal duration of the hormonotherapy , the use of the bicalutamide 150 mg instead of GnRH agonists, the optimal radiation dose. Radical prostatectomy is no more considered as a standard treatment for these patients. Since the use of chemotherapy for metastatic patients showed a benefit in overall survival, the place of chemotherapy as adjuvant or neo-adjuvant treatment is questionned in several randomized phase III studies. Sometimes high-risk disease is diagnosed after performance of a radical prostatectomy. A postoperative radiation may be performed in order to decrease clinical and biochemical progression. The use of bicalutamide 150 mg in this situation may have a positive impact too on progression free survival. In case of lymph node involvement, androgen deprivation is the standard treatment with an overall survival benefit. The place of local radiation therapy is still debating.

Isolated lymph node relapse of epithelial ovarian carcinoma: outcomes and prognostic factors.

BACKGROUND: Relapses of epithelial ovarian carcinoma (EOC) have a poor prognosis. Isolated lymph node relapses (ILNR) are considered of relatively good prognosis with intensive therapy. METHODS: This retrospective study aimed to describe incidence, characteristics, outcomes and prognostic factors of ILNR treated over 15 years. RESULTS: Twenty-seven patients (4.2%) experienced an ILNR among 640 patients. Median age was 59 years, tumour stages included stage I (n=4), II (n=5), III (n=15) and IV (n=3). After initial optimal treatment, median progression-free survival (PFS) was 26 months. Sites of relapse were retroperitoneum (n=15), left supraclavicular (n=7), mediastinum (n=4), iliac (n=4) and inguinal (n=3). ILNR locations were unique in 63% of patients (n=17) and multiple in 37% (n=10). Treatment modalities were surgery in eight patients (30%), chemotherapy in 15 (55%) and radiotherapy in 5 patients (18%), alone or in combination. Seven patients without tumour-related symptoms (26%) were not treated. Median overall survival (OS) after ILNR was 26 months. Median OS from initial diagnosis was 68 months. 25% of patients had a very long survival (>100 months), independent of their initial staging or PFS. There was no difference in 2-year survival after ILNR between the groups of early relapse (before 24 months) and late relapse (after 24 months). In the seven non-treated patients, median OS was 91 months. CONCLUSION: ILNR is a rare event in EOC. Time to relapse may not have its usual prognostic value. Immediate or delayed therapy should be discussed in case of asymptomatic ILNR.