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Recurrent respiratory papillomatosis (RRP) is a currently incurable benign neoplasm caused by human papilloma virus (HPV) infection. It usually reduces voice, respiratory, and general quality of life, and is sometimes life-threatening. Patients usually need repeated operations. The use of adjuvant bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A, has been described in several case reports, with a good efficacy and safety profile. We report the cases of five patients with aggressive RRP who were treated with adjuvant systemic bevacizumab in a single Belgian tertiary center. A complete response was achieved in four patients after a median of 4.5 months, and a partial response in one. In all cases, the number of surgeries was drastically reduced, and quality of life improved. Toxicity was easily managed. Systemic bevacizumab seems to be an effective and safe adjuvant treatment for aggressive RRP.

Predictive factors for adverse events in metastatic colorectal cancer patients treated with regorafenib are currently lacking. In this safety analysis of a prospective phase II clinical trial, we assess the association between several clinical, laboratory, and imaging parameters and the occurrence of adverse events. Our results show that female sex is an independent risk factor for increased toxicity. Background: Regorafenib is a standard treatment for refractory metastatic colorectal cancer (mCRC). In view of the toxicity burden, significant research efforts have been made to increase the therapeutic ratio of this multikinase inhibitor. Predictive factors for treatment-related adverse events (TRAEs), however, are still lacking. Materials and Methods: We assessed the association between a number of baseline clinical, laboratory and imaging parameters and the occurrence of TRAEs in 136 patients who had received regorafenib (160 mg/day, 3-weeks-on/1-week-off) in a prospective phase II clinical trial. Results: Grade >= 2 TRAEs during the first cycle of treatment (84% vs. 60%, P=.002) and grade >= 3 TRAEs throughout the whole treatment (71% vs. 53%, P=.035) occurred more frequently in females, with sex being the only independent predictive factor of early and any-time toxicity (OR 3.4; 95% CI: 1.2-11.1, P=.02 and OR 2.1; 95% CI: 1.0-4.4, P=.045, respectively). Fatigue, anorexia, hypertension, and rash were reported significantly more frequently by females than males (P

Background The survival of colorectal cancer patients is frequently determined by the extent of metastatic invasion to the liver; in cases of major involvement, therapeutic strategies are limited because the liver is necessary for drug metabolism. Material and methods We have reviewed articles about the pharmacokinetic profiles of each drug used in colorectal cancer patients with hepatic dysfunction to determine which of these treatments are most feasible. Results Some drugs appear to be feasible options for patients with hepatic insufficiency. Agents such as 5-fluorouracil and oxaliplatin, as well as monoclonal antibodies such as bevacizumab, cetuximab, and panitumumab, can potentially be used in these cases. On the other hand, irinotecan and regorafenib cannot be recommended because of the risk of increased toxicity. Conclusion Treatment of patients with colorectal cancer and liver dysfunction represents a major challenge because the prognosis is usually very poor and alteration of liver function is normally an exclusion criterion in clinical trials. In this review, we present evidence regarding the use of each drug in patients with colorectal cancer and hepatic impairment.

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.

Background: This phase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinum-based therapy. Patients and methods: Thirty-seven patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity. The primary end point was the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. Angiogenesis-related proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control. Results: Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with noncontrolled disease, we observed in patients with controlled disease a significant higher baseline level of angiopoietin-1 and a significant early plasma decrease in angiopoietin-1, endoglin,and platelet-derived growth factor-AB. PTEN loss was observed only in patients with PD. Conclusions: Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.

Background: Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. Methods: Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m−2 plus irinotecan 250 mg m−2 (Day 1)) or 3-weekly DF (docetaxel 85 mg m−2 (Day 1) followed by 5-fluorouracil 750 mg m−2 per day as a continuous infusion (Days 1–5)). Results: A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3–4 neutropenia, febrile neutropenia and diarrhoea were more frequent in the DI arm as compared with the DF arm (83.3% vs 69.8%, 40.5% vs 18.6%, and 42.9% vs 16.3%, respectively). Conclusion: Both docetaxel-based doublet regimens show comparable efficacy; however, the DF regimen was associated with a better toxicity profile and is an alternative treatment option for patients in whom platinum-based regimens are unsuitable.

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.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.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) was6 months in the majority (n = 50/55) of patients, five patients (9.2%) had a PFS on cetuximab of9 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.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.

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.

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.

Circadian rhythms exist for hematopoiesis, but little is known about circadian variation of bone marrow engraftability and host “acceptability”. Using a B6.SJL to C57BL/6J congenic transplant model, we chose 3-times with light on: Hours After Light Onset (HALO) 4, 8, and 12 and 3-times with light off: HALO 16, 20, and 24. The mice were conditioned on a 12-h light/dark cycles. Recipient mice (100 cGy) received 40 million cells. We demonstrated a significant variation of bone marrow engraftability into bone marrow, spleen, and thymus when donor animals were subjected to changes in their light/dark cycles. Two statistically significant nadirs in all three organs were observed at HALO 8 and 24 in experiments carried out in July, while an identical set of experiments in February analyzing engraftment in marrow and spleen showed nadirs at HALO 8, but not at HALO 24. Marrow progenitors from the July experiments showed nadirs at HALO 12 and 24. The percentage of progenitors in S phase peaked at HALO 8 and 24. Interestingly, there were no changes in the ability of host to accept grafts with changes in the light/dark cycles of host animals. Circadian variations of bone marrow engraftability are important and should be considered in bone marrow transplant strategies. © 2004 Wiley-Liss, Inc.

Summary. Graft rejection and graft-versus-host disease are major problems in mismatched marrow transplants along with toxicity from standard myeloablative host treatments. We have established a tolerization model, using 1 Gy irradiation, which reduces stem cell capacity to

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/m2 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 ≥ 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.

BACKGROUND: Bilateral testicular neoplasia is rare, with an incidence ranging from 1 to 5%. Long-term survival has improved in recent years due to advanced diagnostic approaches and new therapeutic methods that are highly effective against germ cell tumors. CASE PRESENTATION: We present the case of a patient with a primary seminomatous testicular tumor, who developed a contralateral metastasis and a subsequent metachronous tumor following chemotherapy and consolidation radiotherapy treatment. CONCLUSIONS: Strict follow-up, including physical examination and ultrasound examination of the contralateral testis, enabled early diagnosis of the second tumor, giving the patient a high likelihood of a definitive cure.

Background Cholangiocarcinomas are rare tumors, and metastasis to the intramedullary spinal cord is also rare. To the best of our knowledge, this is the first case of simultaneous cholangiocarcinoma and intramedullary spinal cord metastasis to be described in the medical literature. Case presentation A 62-year-old Caucasian male with a cholangiocarcinoma presented pain around his left shoulder without any other symptoms. The results by magnetic resonance imaging and F18 fluorodeoxyglucose positron emission tomography/computer tomography revealed an intramedullary metastasis at the C4 level, with spinal cord compression, and numerous secondary parenchymal brain metastases. Conclusion This patient was treated successfully with a combination of radiotherapy, corticosteroids, and chemotherapy. He experienced complete relief of the symptoms and showed improvements upon subsequent radiological evaluations.