High-dose calcitriol, docetaxel and zoledronic acid in patients with castration-resistant prostate cancer: a phase II study.

INTRODUCTION: Docetaxel has become the standard chemotherapy for patients with castration-resistant prostate cancer (CRPC). We wanted to assess the efficacy and safety of a weekly high-dose calcitriol, docetaxel and zoledronic acid combination in CRPC. PATIENTS AND METHODS: Thirty patients were enrolled to receive calcitriol 0.5 µg/kg orally in 4 divided doses over 4 h on day 1 of each treatment week, docetaxel 36 mg/m(2) i.v. infusion on day 2 of each treatment week and zoledronic acid 4 mg i.v. on day 2 of the first and fifth week of each cycle. Treatment was administered weekly for 6 consecutive weeks on an 8-week cycle. RESULTS: Out of 23 evaluable patients, there was a response of prostate-specific antigen (PSA) in 11 patients (47.8%); 6 (26.1%) had a stable PSA level for a median of 4.2 months. The median survival time was 15 months (95% confidence interval 13.9-16.1 months). The regimen was generally tolerated; anemia was the only grade 3/4 hematological toxicity in 2 patients. CONCLUSIONS: This regimen was tolerated, and half of the patients had a PSA response. Although our response rates are inferior to some studies using docetaxel, we believe our response rates are acceptable knowing that we are treating CRPC, which still has variable outcomes.

Platinum-based compounds for the treatment of metastatic breast cancer.

The role of platinum-based compounds (PBCs) in the treatment of metastatic breast cancer (MBC) has been extensively studied. As single agents, high response rates have been observed in first-line therapy, while results in pretreated patients were discouraging. Regimens containing cisplatin/carboplatin together with taxanes showed the highest efficacy and safety as both first-line and second-line therapy. When administered with vinorelbine, the combination was also active and well tolerated in anthracycline- and taxane-pretreated patients. Combining PBCs with etoposide or nucleoside analogues showed moderate activity, yet high toxicity in the case of etoposide. The overall results for the combination with anthracyclines were disappointing. Addition of trastuzumab to PBC combinations showed remarkable activity and good tolerability in patients with HER2/neu overexpression. The use of cisplatin or carboplatin alongside novel targeted therapeutics for patients with triple-negative MBC seems promising and is being further evaluated. The use of PBCs against MBC requires careful patient selection and combination with the right chemotherapeutic agent.

Pulmonary hypertension in children and young adults with sickle cell disease: evidence for familial clustering.

BACKGROUND: Pulmonary hypertension (PHTN) is increasingly recognized as a serious complication of sickle cell disease (SCD). Our objective was to determine the prevalence of PHTN and identify factors associated with PHTN among children and young adults with SCD in Lebanon. PROCEDURE: From June 2004 to June 2008, 90 patients were studied. Correlation of TRV with LDH, mean corpuscular volume (MCV), fetal hemoglobin (HbF), hydroxyurea use, and G6PD deficiency was performed. Transthoracic Doppler echocardiography was performed during steady-state at each patient's initial visit and yearly thereafter. PHT was defined as a tricuspid regurgitant jet velocity (TRV) > or =2.5 m/sec. RESULTS: Twenty-seven patients (31.8%) were found to have PHTN. They had significantly higher LDH levels (P = 0.008) and MCV (P = 0.024). There was a higher percentage of patients on hydroxyurea in the group with PHTN (78% vs. 50%, P = 0.015). Furthermore, five children, mean age 9.8 years (range, 6-13 years), with initially normal TRV developed PHTN while on hydroxyurea for at least 3 years, at a mean dose of 19.2 mg/kg/day (range, 14-24). PHTN clustered in families and was found in all members with SCD in 7 of the 21 families studied; they contributed 16 of the 27 patients with PHTN. None of the 21 patients with PHTN were G6PD deficient compared to 4 of 36 without PHTN. CONCLUSIONS: PHTN was common, associated with increased hemolysis but not G6PD deficiency, and clustered in families. Moreover, PHTN developed despite hydroxyurea therapy in five patients.

Current Status of Cancer-Related Pain and Opioid use in South Lebanon: A Pilot Study.

OBJECTIVE: This study aimed to evaluate the patients and health providers' (doctors and nurses) knowledge and understanding of the disease-related pain, and the perception of pain drugs (opioids) in South Lebanon. PATIENTS AND METHODS: This was a pilot study conducted at different hospitals in South Lebanon among patients with confirmed cancer diagnosis and providers. Data was collected using patients' and providers' questionnaires. RESULTS: 43 patients and 42 providers were included. 22 (52%) patients were male. Nine (21%) patients were aware of their diagnosis and only 60% talked about their pain to their oncologist. Pain was not optimally controlled with 25 (58%) patients having uncontrolled pain and 18 (42%) patients having continuous pain. Morphine was negatively perceived with 55.8% of patients believing that morphine causes addiction and 59% taking pain medications only when the pain is maximal. This led to a 58% short duration control of intermittent pain. 60% of the providers were certain that cancer pain cannot be relieved by morphine while only 33% believed that morphine can cause complete relief. Addiction seemed to be the main obstacle for morphine use with 37 (89%) thinking that narcotics causes addiction and 51% considering morphine withdrawal if side effects appear. Finally, 30% suggested to discontinue morphine in the terminal stages of cancer. DISCUSSION AND CONCLUSION: Major misconceptions in cancer patients are observed in the approach to antalgic treatment in our population. With good education, better knowledge and optimal palliative care units, misconceptions about opioids can be corrected with best management of cancer pain.

Tongue carcinoma in an adult Down's syndrome patient: a case report.

BACKGROUND: Cancer of the oral cavity is rare and unusual in Down's syndrome patient. The over all risk is similar to that in adult population. CASE PRESENTATION: This case report describes a 27 years old male with Down's syndrome, non-smoker, who developed a poorly differentiated squamous cell carcinoma of the tongue. The patient underwent a hemiglossectomy without neck dissection followed by a postoperative locoregional radiation therapy to a total tumor-bed dose of 56 Gy and 45 Gy to the neck. Three months later, the patient presented with local tongue recurrence and was treated by Docetaxel and Carboplatin chemotherapy with no significant response. The patient died one month later, 9 months after his initial diagnosis. CONCLUSION: To our knowledge, this is the first case of tongue carcinoma arising in a patient with Down's syndrome. This unique case might not be sufficient to make a significant conclusion on the prognosis and survival of these patients but will increase the awareness about this possibility and will help in the appropriate management of Down's syndrome patients.

Docetaxel and irinotecan as first-line chemotherapy in patients with advanced non-small-cell lung cancer: a pilot study.

AIMS: The aim of this study is to evaluate the activity and toxicity of the combination docetaxel and irinotecan as first-line therapy for advanced non-small-cell lung cancer (NSCLC). MATERIALS & METHODS: Twenty-two chemotherapy-naive patients with stage IIIB with pleural effusion or stage IV NSCLC received irinotecan 50 mg/m2 on days 1, 8, and 15, and docetaxel 50 mg/m2 on day 2, every 28 days until disease progression. RESULTS: Median follow-up was 10 months (range: 2-28 months). The overall response rate was 36.4% (8/22 patients; 95% confidence interval: 16.8-56.0), with no complete responses. Median time to disease progression was 5 months (range: 1-24 months) and median overall survival was 10 months (range: 2-28). Grade 3-4 diarrhea was observed in 2 patients (9.1%). Grade 3-4 neutropenia occurred in 2 patients (9.1%): 1 episode of febrile neutropenia in one patient, and 1 death due to neutropenic sepsis in another patient. One patient received transfusion for grade 4 anemia. CONCLUSIONS: Irinotecan showed a moderate response rate and overall survival of clinical interest. Diarrhea was the main toxicity. This regimen may be suitable for patients unable to tolerate cisplatin-based therapy, for elderly and/or for patients with poor performance status, and should be investigated in a larger trial.

Oral vinorelbine plus cisplatin followed by maintenance oral vinorelbine as first-line treatment for advanced non-small cell lung cancer.

PURPOSE: Vinorelbine plus cisplatin is a commonly used doublet for the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy of oral vinorelbine as maintenance therapy in advanced NSCLC. METHODS: This multicenter phase II open-label, non-comparative study was designed to evaluate the three-weekly combination of cisplatin 80 mg/m(2) on day 1 in combination with oral vinorelbine on day 1 and 8 in advanced NSCLC. RESULTS: Thirty-nine patients were enrolled; median age was 63 years (range 42-82). In the response-evaluable population (n = 38), objective response after induction therapy was observed in 18 (47 %) patients with two (5 %) patients achieving complete response. Stable disease was observed in nine (24 %) patients. The median duration of response was 6 months. Eighteen (46 %) patients received oral vinorelbine as maintenance therapy. The median PFS for the whole population and for the maintenance therapy group was 4.9 [95 % CI (2.8-6.9)] and 6.7 [95 % CI (3.7-9.7)] months, respectively, while the overall survival was 8.7 [95 % CI (5.4-11.9)] and 11 [95 % CI (8.3-13.7)] months, respectively. The main observed overall hematologic toxicities were grade 3 anemia (8 %) and grade 3/4 neutropenia (8 %). CONCLUSION: Maintenance therapy with single-agent oral vinorelbine is feasible and well tolerated; it seems to extend the efficacy of the combination regimen with the advantage of being convenient to patients.

Hypertension induced by chemotherapeutic and immunosuppresive agents: a new challenge.

BACKGROUND: Hypertension is a common adverse effect of certain anti neoplastic therapy. The incidence and severity of hypertension are dependent mainly on the type and the dose of the drug. METHODS: We reviewed the literature for studies that reported the effect of anti neoplastic agents on blood pressure in patients with malignancies. The medical databases of PubMed, MEDLINE and EMBASE were searched for articles published in English between 1955 and June 2012. The effects of specific agents on blood pressure were analyzed. RESULTS AND CONCLUSIONS: Hypertension is a prevalent adverse effect of many of the new chemotherapy agents such as VEGF inhibitors. Approximately 30% of patients treated for cancer will have concomitant hypertension, and crucial chemotherapy can sometimes be stopped due to new onset or worsening severe hypertension. The importance of a timely diagnosis and optimal management of HTN in this group of patients is related to the facts that HTN is a well established risk factor for chemotherapy-induced cardiotoxicity and if left untreated, can alter cancer management and result in dose reductions or termination of anti-cancer treatments as well as life-threatening end organ damage.

A nationwide non-interventional epidemiological data registry on myelodysplastic syndromes in Lebanon.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by peripheral blood cytopenias, blood cells dysplasia, and increased risk for progression to acute leukemia.Physicians should be vigilant in diagnosing MDS and should be aware of the contemporary therapies that are always in progress. Most of the data on MDS epidemiology and management comes from developed countries. The incidence and features of MDS in the Arab countries, among them Lebanon, are not known. We undertook a nationwide epidemiological registry study of all newly diagnosed MDS cases through 2010-2011. Patients were referred by 21 hematologists/oncologists practicing in 17 hospitals and medical centers distributed across the entire country. 58 patients (29 males and 29 females) with confirmed MDS were included. The calculated incidence rate of MDS was 0.71 per 100,000 people. The median age at diagnosis was 73 years (range 16-86). The most common complaints on presentation were fatigue (70.7%), weakness (60.3%) and pallor (43.1%). Most patients were diagnosed as refractory anemia with excess blasts (RAEB; 36.2%) and refractory cytopenia with multilineage dysplasia (RCMD; 32.8%). This paper constitutes the first epidemiological report on the incidence and specific subtypes of MDS in Lebanon.

Gemcitabine plus carboplatin combination therapy as second-line treatment in patients with relapsed breast cancer.

This study was designed to determine the safety and efficacy of the combination therapy of gemcitabine plus carboplatin when used as a second-line treatment in patients with metastatic breast cancer (MBC). From February 2002 to May 2003, 30 previously treated patients with adenocarcinoma of the breast received gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin to an area under the curve (AUC) of 5 on day 1. The carboplatin dose was changed to an AUC of 4.5 because of toxicity, with cycles repeated every 3 weeks. Among 30 patients enrolled, 25 were assessable for response rate (RR). There was no complete response; 9 patients (30%) had partial response, for an overall RR of 30%. The median time to progression for the study group was 20.47 weeks (range, 8-46 weeks). Treatment-related toxicities included grade 3/4 neutropenia in 50% of patients (20% of whom had febrile neutropenia), grade 3/4 anemia in 26.6% of patients, and grade 3/4 thrombocytopenia in 30%. Eleven patients (36.67%) had grade 1 alopecia, and 1 patient (3.33%) had grade 2 alopecia. Moderate nausea was observed in 8 patients (26.67%), and vomiting occurred in 7 patients. Four patients had asthenia and 3 (10%) experienced stomatitis. Three patients discontinued treatment because of hematologic toxicity (thrombocytopenia) and 2 patients are still receiving treatment. Carboplatin plus gemcitabine is an active combination for patients with MBC despite significant but manageable hematologic toxicity.

Cutaneous manifestations of anti-angiogenic therapy in oncology: Review with focus on VEGF inhibitors.

The role of the VEGF signaling pathway in angiogenesis has been extensively investigated, and many new targeted anti-angiogenic drugs have evolved from this knowledge. The recent approval and introduction of these anti-neoplastic drugs has revolutionized the treatment of many types of cancers, but has also revealed numerous toxicities to the skin and its adnexae. Since these cutaneous side effects may have a significant impact on the physical, emotional and psychosocial health of patients, it is important for dermatologists and oncologists alike to be aware of the cutaneous complications of these drugs in order to properly diagnose and treat them. This review will detail the presentation of the cutaneous complications of the anti-angiogenic drugs, most notably bevacizumab, sorafenib and sunitinib, and shed light on the management of such adverse reactions.

Targeted therapies in non-small cell lung carcinoma: what have we achieved so far?

The search for innovative therapeutic agents in non-small cell lung cancer (NSCLC) has witnessed a swift evolution. The number of targeted drugs that can improve patient outcomes with an acceptable safety profile is steadily increasing. In this review, we highlight current drugs that have already been approved or are under evaluation for the treatment of patients with NSCLC, either in monotherapy or combined therapy for both the first- and second-line settings. Experience with drugs targeting the vascular endothelial growth factor and its receptor, as well as the epidermal growth factor receptor is summarized. Moreover, we provide an overview of more novel targets in NSCLC and initial experience with the respective therapeutic agents.

A collaborative nationwide lymphoma study in Lebanon: incidence of various subtypes and analysis of associations with viruses.

Incidence of various Hodgkin (HL) and non-Hodgkin lymphoma (NHL) subtypes and association with viruses in Lebanon are not known. We undertook a nationwide study of 272 patients diagnosed with lymphoma in 2007. HL comprised 32.7 % (n = 89) of cases while NHL represented 67.3 % (n = 183). Consistent with the literature, nodular sclerosis was the most predominant HL subtype (n = 57/89). Among NHL, B-cell NHL represented 88 % (n = 161/183), T-cell NHL 9 % (n = 17/183), whereas in 2.7 % it was not classifiable. The B-cell NHL comprised predominantly diffuse large B-cell lymphoma (46 %) and follicular lymphoma (23 %). 81 cases were reviewed by a panel of pathologists with 87.6 % concordance rate. Serology was negative for hepatitis C in 122 tested cases. HIV was positive in 2 cases. Two adult T-cell leukemia/lymphoma were HTLV-I positive. EBV IgG were positive in 88.5 % of cases. 38 EBV seropositive cases [27 NHL (24 B-cell, 3 T-cell) and 11 HL] were studied for EBV genome expression using EBV-encoded RNA (EBER)-in situ hybridization. EBER expression was positive in 8 (21 %) cases (6 HL, 2 T-cell NHL). The distribution of lymphoma subtypes in Lebanon appears similar to that of Western countries. The high rate of EBV positivity in HL and T-cell lymphoma by EBER deserves further investigation.

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer.

OBJECTIVE: Gemcitabine and platinum-based compounds represent the new standard combination therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gemcitabine and carboplatin followed sequentially by paclitaxel in 27 patients with advanced transitional cell carcinoma. METHODS: This phase II multicentre study was based on the doublet gemcitabine 800 mg/m2 and carboplatin area under the concentration-time curve 2 on days 1 and 8 every 21 days for 4 cycles, followed sequentially by paclitaxel 60 mg/m(2)/w for 12 consecutive weeks. The disease was assessed after each sequence. RESULTS: Primary tumor was localized in the bladder and renal pelvis in 25 and 2 patients, respectively. Twenty patients completed all 4 cycles of the gemcitabine and carboplatin sequence. Mean number of cycles was 3.5 (range 1 to 4). Toxicities were mainly hematologic, including Grade 3 neutropenia and anemia in 3 patients. OBJECTIVE response was noted in 11 pts (40.7%), including 1 complete response (CR) and 10 partial responses (PR). Three patients had stable disease and 11 progressed. Among the 20 patients, 14 received the second sequence. Mean number of paclitaxel injections was 7 (range 2 to 12). Toxicities were limited to diarrhea and neurotoxicity in 1 patient each. OBJECTIVE response was documented in 6 patients (30%) (3 CR and 3 PR), including the improvement of PR into CR in 2 patients. Median duration of response was 6 months. After a median follow-up of 7 months, 21 patients died and 6 remained alive, including 2 who maintained CR and 1 PR.Sixteen patients had locally advanced disease and 11 had metastatic disease, better prognostic was noticed with patients with locally advanced disease. CONCLUSION: the sequential approach of treatment for advanced urothelial cancer using gemcitabine and carboplatine followed by paclitaxel seems to be a safer alternative to the combined triplet, but due to the limited number of patients this study failed to improve outcome. Further investigations with larger population are required.

Expression, prognostic and predictive impact of VEGF and bFGF in non-small cell lung cancer.

Despite major advances in cancer therapeutics, the prognosis for lung cancer patients is still poor and the median survival for patients presenting with advanced non-small cell lung cancer (NSCLC) is only 8-10 months. Angiogenesis is an important biological process and a relatively early event during lung cancer pathogenesis. Anti-angiogenic agents are used in treating patients with NSCLC, and their molecular biomarkers are also being assessed to predict response. A better understanding of the biology of angiogenesis in NSCLC may reveal new targets for treating this malignancy. In this article, we review the expression and prognostic impact of the angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor, in NSCLC.

A phase II study of lipoplatin (liposomal cisplatin)/vinorelbine combination in HER-2/neu-negative metastatic breast cancer.

UNLABELLED: We assessed the efficacy and safety of a liposomal cisplatin (lipoplatin) and vinorelbine combination in metastatic breast cancer (MBC). Thirty-five patients were treated. The objective response rate was 53.1% and the median survival time was 22 months. Grade 3/4 neutropenia was observed in 44% of cycles, and febrile neutropenia was seen in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. This combination is effective and well tolerated in patients with MBC and it warrants investigation as first-line treatment. BACKGROUND: Liposomal cisplatin (lipoplatin) has a mechanism of action similar to that of cisplatin, with reduced toxicities and enhanced or similar efficacy. We wanted to assess the efficacy and safety of a lipoplatin/vinorelbine combination in a phase II clinical trial in metastatic breast cancer (MBC). METHODS: Thirty-five patients with HER-2/neu-negative (HER-2/neu(-)) MBC were enrolled. Lipoplatin 120 mg/m(2) (days 1, 8, and 15) and vinorelbine 30 mg/m(2) (days 1 and 8) were administered in a 21-day cycle. RESULTS: Thirty-five patients were included in the intent-to-treat (ITT) analysis; 32 patients were evaluable for response. The objective response rate was 53.1%. Complete response (CR) was achieved in 3 patients (9.4%), partial response (PR) was seen in 14 patients (43.8%), stable disease (SD) was obtained in 12 patients (37.5%), and progressive disease (PD) was seen in 3 patients (9.4%). Median time to disease progression was 8 months (range 6-10 months). After a median follow-up of 15.5 months, 18 patients were still alive; the median survival time was 22 months (95% confidence interval [CI], 14-30). A total of 174 cycles were administered. Neutropenia was the most frequent hematologic toxicity, with grade 3/4 neutropenia observed in 44% of cycles. Febrile neutropenia was observed in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. Grade 1/2 nephrotoxicity occurred in 8 patients (22.9%) and grade 3 vomiting was seen in 3 patients (8.6%). CONCLUSIONS: The results of this trial reveal that vinorelbine/lipoplatin is effective in treating patients with MBC. This regimen is well tolerated with no grade 3/4 nephrotoxicity or neuropathy. The investigation of this regimen as first-line treatment in MBC is warranted.

Role of capecitabine and irinotecan combination therapy in advanced or metastatic gastric cancer.

Gastric cancer is one of the most common cancers and the second leading cause of cancer-related death. So far, the only curative treatment for gastric cancer is surgery. However, approximately half of all patients present with nonoperable tumors. Therefore, combination chemotherapy regimens are being accepted nowadays as first-line treatment for this disease. Despite the numerous efforts of randomized trials on advanced gastric cancer, no globally accepted regimen has yet been established. Historically, the most widely adopted protocols use 5-fluorouracil or platinum-based therapy with a response rate not exceeding 50% in combination therapy with a high rate of toxicity. Recently, many new drugs have emerged on the market and have been used in treating advanced or metastatic gastric cancer allowing the creation of new combination regimens with better clinical benefit. The combination of irinotecan plus capecitabine is one of these new combinations that seem to provide an acceptable response rate and good toxicity profile. In this article, we review the efficacy, tolerability, and feasibility of this combination for the treatment of advanced or metastatic gastric cancer and we summarize the clinical trials using this regimen.

Role of low dose capecitabine combined to irinotecan in advanced and metastatic gastric cancer.

Chemotherapy has a proven role in advanced and metastatic gastric cancer (AMGC) significantly improving quality of life and prolonging survival compared with best supportive care alone. Multiple regimens have been explored. The choice of treatment should be individualized and tailored to the patient's overall conditions and preference. This manuscript is divided into two sections. The first section illustrates the results of a phase II trial combining weekly irinotecan and low dose capecitabine in the management of untreated AMGC patients. The second section aims to identify the current optimal place of this combination in the management of AMGC in the light of the latest advances. In this manuscript we detail our phase II trial which showed objective response rate of 47% (15 patients), disease stabilization of 28% (9 patients), and overall tumor control rate of 75% (24 patients). Median time to progression and overall survival were 5.8 and 8 months, respectively. Grades III-IV toxicities were reported in 7 cases. Low-dose capecitabine plus irinotecan is effective in the treatment of AMGC with an acceptable toxicity profile. Compared to the recent published data, this combination is indicated in the second-line treatment of AMGC and in the first-line treatment where a contraindication for docetaxel- and/or oxaliplatin-based regimen is present.