Lionel D'Hondt

Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma

BACKGROUND To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with recurrent high-grade glioma (HGG) after failure of surgery, radiation therapy, and chemotherapy. PATIENTS AND METHODS In this two-arm, open-label, phase II study patients were stratified according to their epidermal growth factor receptor (EGFR) gene amplification status. Cetuximab was administered intravenously at a dose of 400 mg/m(2) on week 1 followed by weekly dose of 250 mg/m(2). The primary end point for this study was the response rate in both study arms separately. RESULTS Fifty-five eligible patients (28 with and 27 without EGFR amplification) tolerated cetuximab well. Three patients (5.5%) had a partial response and 16 patients (29.6%) had stable disease. The median time to progression was 1.9 months [95% confidence interval (CI) 1.6-2.2 months]. Whereas the progression-free survival (PFS) was <6 months in the majority (n = 50/55) of patients, five patients (9.2%) had a PFS on cetuximab of >9 months. Median overall survival was 5.0 months (95% CI 4.2-5.9 months). No significant correlation was found between response, survival and EGFR amplification. CONCLUSIONS Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.

Prospective Randomized Study Comparing Docetaxel, Estramustine, and Prednisone With Docetaxel and Prednisone in Metastatic Hormone-Refractory Prostate Cancer

PURPOSE To assess the efficacy and toxicity of the addition of estramustine to docetaxel (D) for the treatment of metastatic hormone-refractory prostate cancer. PATIENTS AND METHODS One hundred fifty patients were randomly assigned to D alone (35 mg/m(2) on days 2 and 9, every 3 weeks) or D in combination with estramustine (D/E; 280 mg orally three times a day on days 1 to 5 and 8 to 12, every 3 weeks). All patients received prednisone (10 mg/d). The primary end point was prostate-specific antigen (PSA) response rate, which was defined as a decrease in PSA > or = 50% from baseline. The study was powered to test the hypothesis that D/E would improve the PSA response rate by 25%. RESULTS The PSA response rate was not statistically different between the two groups. PSA of less than 4 ng/mL occurred in 29 (41%) of 71 patients receiving D/E and in 17 (25%) of 69 patients receiving D (P = .05). No significant differences were found for median time to PSA progression (D/E, 6.9 months; D, 7.3 months) or median overall survival time (D/E, 19.3 months; D, 21 months). More patients had at least one grade 3 or 4 toxicity with D/E (45%) compared with D (21%; P = .005), mainly as a result of grade 3 or 4 GI toxicity (P = .05). Serious adverse events were more frequent with D/E (n = 20) than with D (n = 9; P = .04). CONCLUSION The addition of estramustine to weekly D does not provide any clinically relevant advantage. Both regimens are well tolerated, although the toxicity profile favors D without estramustine.

MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma

AIMS To investigate the correlation between O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma. PATIENTS AND METHODS A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence. RESULTS A subgroup of 38 patients who were chemotherapy-naive at recurrence was analysed (22 glioblastoma, 12 anaplastic astrocytoma [AA] and 4 anaplastic oligoastrocytoma [AOA]); none had 1p/19q loss. Among 10 (26%) patients with a hypermethylated MGMT promoter, none experienced disease progression within the first two treatment cycles compared with 12 of 28 (43%) patients with an unmethylated promoter (p=0.016). By Cox multivariate analysis, tumour grade and MGMT promoter methylation correlated with time to progression (p<0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma. CONCLUSIONS MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence.

A Multicenter Cohort Study of Dose-Dense Temozolomide (21 of 28 Days) for the Treatment of Recurrent Anaplastic Astrocytoma or Oligoastrocytoma

Dose-dense temozolomide schedules deplete O6-methylguanine methyltransferase and may overcome chemoresistance. This multicenter cohort study enrolled 19 patients (15 anaplastic astrocytoma, 4 anaplastic oligoastrocytoma) who received temozolomide (100 mg/m2/day for 21 consecutive days every 28-day cycle) at first recurrence, either until disease progression or 12 cycles. Six-month progression-free survival was 56%, comparing favorably with historic controls treated with the standard 5-day temozolomide schedule. Median survival was 12.9 months (95% CI: 3.7, 22 months). Among 15 evaluable patients, 2 had a complete or partial response, and 10 had stable disease. Grade 3 and 4 lymphopenia occurred in 53% and 47% of patients, respectively.

Clostridium tertium bacteremia: contamination or true pathogen? A report of two cases and a review of the literature.

We observed two cases of Clostridium tertium bacteremia three months apart in the sterile unit of our department of hematology and oncology. One patient was being treated for first-relapse acute myeloblastic leukemia, while the second was receiving high-dose chemotherapy with hematopoietic stem cell support for non-Hodgkin lymphoma. At the time that C. tertium was identified, the first patient was completely asymptomatic, while the second was highly febrile. Both responded biologically and/or clinically to antibiotherapy. We discuss the epidemiology and pathology of C. tertium in the general and cancer patient population.

Agrobacterium radiobacter bacteremia in oncologic and geriatric patients: presentation of two cases and review of the literature.

INTRODUCTION We report here two cases of Agrobacterium radiobacter bacteremia. These cases were observed at the same institution over a short time period (3 months). CASE REPORTS The first patient was a female cancer patient receiving third-line chemotherapy for ovarian carcinoma. When she developed bacteremia, she was neutropenic and had an indwelling catheter that was removed as part of the treatment. The second case was a geriatric patient admitted from home with bacteremia, clinical signs of septic shock, and concomitant acute cholecystitis. OUTCOME Both patients responded promptly and completely to antibiotherapy. No recurrence was observed.

Potential Interactions with Anticancer Agents: A Cross-Sectional Study

Background: Patients with cancer are particularly susceptible to drug interactions (DIs), but the extent of the problem has received limited attention. We aimed to evaluate the frequency of interactions with anticancer agents in a group of cancer patients. Methods: The study was performed in a Belgian teaching hospital. One hundred and twenty-two patients with solid malignancies were included. A comprehensive drug history was performed by a clinical pharmacist. Three renowned DI compendia were used to identify DIs. Results: Forty-one potential interactions involving an anticancer agent and considered to be clinically significant were identified among 25% of patients. The anticancer drugs mostly involved were cisplatin and methotrexate, and the most frequent co-medications involved were vitamin K antagonists, proton pump inhibitors and diuretics. In the majority of cases, the potential adverse consequence was increased toxicity of the anticancer agent and/or of the co-medication. Less than 10% of DIs were identified by the three compendia. Conclusions: Preventive measures should be taken to avoid increased toxicity or decreased efficacy of the drugs. Most of the time, this simply involves surveillance of biological or clinical parameters. Collaboration with a clinical pharmacist may be useful for the prescribing physician.

Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-Based Therapy

Lessons Learned Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate. This phase II study did not meet its primary endpoint. Cabazitaxel has low activity in SCCHN. The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%). Background. Cabazitaxel is a second-generation taxane that improves the survival of patients with metastatic castrate-resistant prostate cancer following docetaxel therapy. Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. In this randomized phase II trial, we investigated cabazitaxel in patients with recurrent SCCHN. Methods. Patients with incurable SCCHN with progression after platinum-based therapy were randomly assigned to cabazitaxel every 3 weeks (cycle 1, 20 mg/m2, increased to 25 mg/m2 for subsequent cycles in the absence of nonhematological adverse events [AEs] greater than grade 2 and hematological AEs greater than grade 3) or methotrexate (40 mg/m2/week). The patients were stratified according to their performance status and previous platinum-based chemotherapy for palliation versus curative intent. The primary endpoint was the progression-free survival rate (PFSR) at 18 weeks. Results. Of the 101 patients, 53 and 48, with a median age of 58.0 years (range, 41–80), were randomly assigned to cabazitaxel or methotrexate, respectively. The PFSR at 18 weeks was 13.2% (95% confidence interval [CI], 5%–25%) for cabazitaxel and 8.3% (95% CI, 2%–20%) for methotrexate. The median progression-free survival was 1.9 months in both arms. The median overall survival was 5.0 and 3.6 months for cabazitaxel and methotrexate, respectively. More patients experienced serious adverse events with cabazitaxel than with methotrexate (54% vs. 36%). The most common drug-related grade 3–4 AE in the cabazitaxel arm was febrile neutropenia (17.3%). Conclusion. This study did not meet its primary endpoint. Cabazitaxel has low activity in recurrent SCCHN.

A systematic review of the predictive value of (18) F-fluoro-2-deoxyglucose positron emission tomography on survival in locally advanced rectal cancer after neoadjuvant chemoradiation

Treatment of locally advanced rectal cancer (LARC) includes preoperative radiation therapy with or without chemotherapy followed by radical surgery, but the clinical outcome is uncertain. A systemic review was carried out to determine the predictive value of 18F‐fluoro‐2‐deoxyglucose positron emission tomography (18FDG‐PET) for assessing disease‐free (DFS) and overall survival (OS) in LARC.

Which Factors Predict Overall Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Post-Docetaxel?

Background Abiraterone acetate (AA) increases overall survival (OS) in patients with metastatic castration‐resistant prostate cancer (mCRPC) previously treated with docetaxel. However, survival time varies substantially between individuals. Our goal was to identify prognostic factors that better estimate OS. Materials and Methods This is a retrospective multicentric analysis of 368 patients with mCRPC starting AA with prednisone after docetaxel. Cox proportional hazards statistics were applied. A multivariate model was constructed based on significant univariate predictors by using a manual stepwise forward and backward selection strategy. Model performance was determined by using receiver operating characteristic (ROC) curves. Results Univariate analysis identified 20 significant OS predictors. A multivariate model was constructed, based on 220 patients, incorporating 5 independent risk factors for decreased OS at the time of AA initiation: hemoglobin < 12 g/dL (hazard ratio [HR] 2.02), > 10 metastases (HR 1.80), ECOG performance status ≥ 2 (HR 1.88), radiographic progression (HR 1.50), and time since diagnosis < 90 months (HR 1.66, all P < .05). Patients were stratified into 3 groups: good (0‐2 risk factors, median OS 22.6 months), intermediate (3 risk factors, median OS 13.9 months), and poor prognosis (4‐5 risk factors, median OS 6.2 months). The area under the ROC curve based on the event “death by the time of median OS (13.3 months)” was 0.736 (95% confidence interval 0.670‐0.803). Conclusion We identified 5 readily available risk factors independently associated with decreased OS. The resulting model may be used for patient counseling in daily clinical practice, as well as patient stratification in clinical trials. Micro‐Abstract Individual patients’ survival varies greatly in metastatic castration‐resistant prostate cancer. Retrospective analysis of 368 patients treated with docetaxel and starting abiraterone acetate revealed 5 adverse prognostic factors: hemoglobin < 12 g/dL, > 10 metastases, ECOG performance status ≥ 2, radiographic progression, and time since diagnosis < 90 months. A prognostic model stratifies patients into 3 groups with different estimated survival, which can aid in patient counseling.