Jamal Zekri

Cetuximab-based therapy for metastatic colorectal cancer: a meta-analysis of the effect of K-ras mutations.

BackgroundCetuximab has a favorable effect on patients with metastatic colorectal cancer harboring wild K-ras gene. This meta-analysis was planned to quantify the benefit.MethodsA meta-analysis of clinical studies that have used cetuximab-based therapy (CBT) for patients with known K-ras status.ResultsThere were four randomized studies (RS) that compared CBT versus non-cetuximab control (NCC) in 2,292 patients, and six non-randomized studies (NRS) included patients received cetuximab after failure of prior chemotherapy (411 patients). Patients in RS with wild K-ras tumor gained more benefit from CBT vs. NCC. For response rate (RR), the odds ratio was 2.10 (p = 0.0002), while the hazard ratio (HR) for progression-free survival (PFS) was 0.64 (p = 0.04). On the other hand, CBT was associated with an adverse effect on RR and no effect on PFS in mutated K-ras. In all patients who received CBT in RS and NRS, those with wild vs. mutated K-ras demonstrated higher RR (odds ratio 3.72; p < 0.0001). Compared with NCC in three RS, CBT showed significant overall survival (OS) advantage in patients with wild K-ras (HR = 0.68; p = 0.01).ConclusionsThe significant clinical benefit of CBT concerning RR, PFS, and OS was restricted to patients with wild-type K-ras. There is a need to better define potential responders to CBT.

The anti-tumour effects of zoledronic acid

Bone is the most common site for metastasis in patients with solid tumours. Bisphosphonates are an effective treatment for preventing skeletal related events and preserving quality of life in these patients. Zoledronic acid (ZA) is the most potent osteoclast inhibitor and is licensed for the treatment of bone metastases. Clodronate and pamidronate are also licensed for this indication. In addition, ZA has been demonstrated to exhibit antitumour effect. Direct and indirect mechanisms of anti-tumour effect have been postulated and at many times proven. Evidence exists that ZA antitumour effect is mediated through inhibition of tumour cells proliferation, induction of apoptosis, synergistic/additive to inhibitory effect of cytotoxic agents, inhibition of angiogenesis, decrease tumour cells adhesion to bone, decrease tumour cells invasion and migration, disorganization of cell cytoskeleton and activation of specific cellular antitumour immune response. There is also clinical evidence from clinical trials that ZA improved long term survival outcome in cancer patients with and without bone metastases. In this review we highlight the preclinical and clinical studies investigating the antitumour effect of bisphosphonates with particular reference to ZA.

Brentuximab vedotin in pretreated Hodgkin lymphoma patients: a systematic review and meta-analysis

ABSTRACT Objectives: This meta-analysis evaluated the effect of single agent brentuximab vedotin (BV) in patients with relapsed/refractory Hodgkin lymphoma (HL). Patients and methods: A systematic literature search was performed and included studies published from 1st January 2012 to 1st July 2015 investigating BV in patients with relapsed/refractory HL. Data was extracted and reviewed by two investigators then analyzed using the comprehensive meta-analysis version 3 software. Results: 22 out of 4048 screened records met the eligibility criteria. These records included 903 patients. The median age of the cohort was 31 years (range: 26-45). 86% received ≥ 3 previous lines of systemic therapy. 529 (58.7%) and 232 (25.7%) underwent high dose chemotherapy and autologous and/or allogeneic stem transplantation prior of BV respectively. The overall response rate to BV was 62.7% (range: 30-100%). The complete response, partial response, stable disease and progressive disease rates were 31.8%, 35.1%, 19.5% and 11.7% respectively. The one year progression free survival and estimated one year overall survival were 47.6% and 79.5% respectively. Conclusion: In this largest published pooled cohort, BV produces high responses with encouraging progression free and overall survival in relapsed/refractory HL patients. Our results enhance the role of BV in heavily pretreated HL patients.

K-ras in Colorectal Cancer Tumors From Saudi Patients: Frequency, Clinco-pathological Association and Clinical Outcome

Background: K-ras oncogene mutations are confirmed factor for lack of clinical benefit from antibodies target- ing EGFR in patients with colorectal cancer (CRC). Mutations are reported in 40% of CRC tumors in western patients. There is scarcity of data on population from Asia and the Middle East. Aims: This study investigates the frequency and impact of k-ras mutation and the association between clinico-pathological features and K-ras status in Saudi patients with CRC. Patients and Methods: Retrospective review of K-ras status, clinico-pathological characteristics and clinical outcome in 46 patients with CRC. Results: K-ras mutations were identified in 15/46 (32%) tumors, 87% at codon 12 and 13% at codon 13. Gender, site of tumor, stage at diagnosis, differentiation and lymphatic and vascular invasion were tested as potential risk predictors for K-ras status. Only gender was found to be a potential risk factor. Female gender compared to male posed higher signifi- cant chance of wild type status (RR=1.54, 65% CI: 1.07-2.2; P=0.034). K-ras status (mutant vs. wild) did not statistically significantly impact on clinical outcome as measured by development of relapsed disease (80% vs. 81%), median relapse free survival (17 vs. 11 months, P=0.256) and overall survival (not reached in both groups, P=0.59). Conclusion: This relatively small retrospective series shows that rate of K-ras mutation in Saudi patients with CRC is lower than reported in western Caucasian population but close to rates reported in neighboring Asian population. Muta- tions are less frequent in females. In these patients, K-ras mutation status did not significantly impact clinical outcome.

Breaking Bad News: Preferences of Cancer Patients in Saudi Arabia

Background: It is believed in some Middle Eastern (ME) cultures that disclosure of bad news to cancer patients may cause loss of hope. This is often used to justify withholding such news. In this study, we examine cancer patients ‘preference regarding breaking bad news and disease information disclosure to them. Patients and Methods: Nine close ended questions addressing patient’s disclosure preference and one question addressing timing of disclosure to the family were designed in a questionnaire format and were answered by cancer patients in an outpatient setting. Affirmative “Yes” answer indicates preference to be informed of bad news. Results: One hundred patients were recruited and answered the questions. 87% of patients preferred to be informed of their cancer diagnosis. There was no statistically significant effect of age, gender, education level, professional status, diagnosis and stage of disease on this preference. 98% wanted to know of serious news about their health. 60% of patients answered “Yes” to 8 or 9 questions. Age ≥ 50 compared to <50 years was the only factor significantly associated with likelihood of affirmative response to 8 or 9 questions (Chi2 P=0.027). Conclusions: Our study indicates that most cancer patients in Saudi Arabia prefer to know the diagnosis of cancer and any related poor outcomes, and to be involved in decision making throughout the course of their illness. This is in congruence with results of other studies from other parts of the world. Given this accumulating body of evidence, healthcare provider should, whenever possible, keep the patients involved in the decision making process throughout the cancer journey.

Back to life with checkpoint inhibitors in Hodgkin lymphoma

Cancer can escape the immune system through different mechanisms. One of which is the expression of program death ligand-1 (PD-L1). This ligand binds to programmed cell death 1 receptor on activated T cells, subsequently leading to inhibition of the immune response. Nivolumab is a novel antibody that binds to programmed cell death 1 and prevents such immune tolerance. Several recently published clinical trials confirmed the clinical efficacy of single agent nivolumab in pretreated patients with different cancer types. Publications on nivolumab in Hodgkin lymphoma are very scarce. We report on a 30-year-old man with stage IVB Hodgkin lymphoma, who failed nine lines of treatments including high-dose chemotherapy and autologous stem cell transplantation and brentuximab vedotin. He reached a major response after four cycles of nivolumab and got married. The available literature is being reviewed. Pre-treated Hodgkin lymphoma is amenable to novel immunotherapy. Nivolumab induces clinically meaningful responses with excellent tolerance. The drug enriches our treatment options by reviving the immune system response against cancer. Further clinical studies are needed to determine the effectiveness on a large patients’ cohort.

Acute jugular vein thrombosis during rituximab administration: Review of the literature

Rituximab, a chimeric monoclonal antibody is licensed for the treatment of CD20 positive lymphomas. Previous studies have found rituximab, in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, is superior to cyclophosphamide, doxorubicin, vincristine, and prednisone alone in the treatment of diffuse large B-cell lymphoma and many other B-cell lymphomas. Acute hypersensitivity reactions have been reported in patients receiving rituximab infusion and usually manifesting as headache, fever, chills, sweats, skin rash, dyspnea, mild hypotension, and nausea. Acute major venous thrombosis and seizures have not been reported as manifestation of acute hypersensitivity reaction. We report on a 22-year-old woman, who was diagnosed with stage III B CD20 positive B-cell diffuse large B-cell lymphoma. During the first cycle of treatment, she developed grand-mal seizure while receiving rituximab infusion without any other features of acute hypersensitivity reaction. Imaging confirmed new onset jugular vein thrombosis with normal coagulation parameters. These events were managed by anticonvulsants and anticoagulation therapy. The patient completed eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone without rituximab and achieved complete remission. No further complications were noted. To our knowledge, this is the first case in the literature describing grand-mal seizures and acute thrombosis while on rituximab treatment. Clinicians should be aware of this rare side effect, as stopping rituximab can prevent recurrence of these complications.

Breaking Cancer Bad News to Patients With Cancer: A Comprehensive Perspective of Patients, Their Relatives, and the Public—Example From a Middle Eastern Country

Purpose Empowering patients with cancer requires that they be continuously informed about their condition. In some Eastern cultures, this concept is often opposed by caregivers. We aim to compare the extent of disclosure desired by actual and presumed patients with cancer and their relatives in our practice. Methods Nine questions reflecting possible bad news communication to patients from diagnosis to the end of life were designed to investigate the extent of desired disclosure and were answered by 100 patients (cohort I) and 103 accompanying relatives (cohort II) in an outpatient setting. In addition, 103 public participants attending a family medicine clinic (cohort III) each answered the questions from the perspective of a presumed patient (cohort IIIA) and the perspective of a relative (cohort IIIB). The primary end point was affirmative response to six or more questions (AR ≥ 6), reflecting a preference to be informed of the majority (≥ 67%) of possible bad news. Results AR ≥ 6 was reported in 85% of cohort I and 52% of cohort II (χ2 P < .001). On multivariable analysis, AR ≥ 6 showed significant association with being a patient (in cohorts I and II) and having nonmetastatic disease (only in cohort I). In the public cohort, AR ≥ 6 was reported in 91% in cohort IIIA and 63% in cohort IIIB (χ2 P < .001). On multivariable analysis, AR ≥ 6 in cohort III was significantly associated with being a presumed patient and having at least a college education. Conclusion Patients desire disclosure of the majority of cancer-related bad news. This is in contrast to the views and requests of relatives. The public participants would also desire similar disclosure if they were to be diagnosed with cancer.

Time from last chemotherapy to death and its correlation with the end of life care in a referral hospital

Background: A substantial number of cancer patients receive chemotherapy until the end of life (EoL). Various factors have been shown to be associated with receipt of chemotherapy until near death. In this study, we determine our average time from last chemotherapy to death (TLCD) and explore different factors that may be associated with decreased TLCD. Materials and Methods: A retrospective review of medical records of adult cancer patients who received chemotherapy during their illness and died in our hospital between January 2010 and January 2012 was conducted. Chi-square test and t-test were used to examine the correlation between selected factors and use of chemotherapy within 60 days of death. Multivariate analysis was used to test independent significance of factors testing positive in univariate analysis. Kaplan-Meier method was used to perform survival analysis. Results: Of the 115 cancer patients who died in the hospital, 41 (35.6%) had TLCD of 60 days or less. Patients with better performance status and those dying under medical oncology service were more likely to be in this group of patients. Univariate analysis showed that these patients were less likely to have palliative care involvement, were more likely to die of treatment related causes, and more likely to have died in the Intensive Care Unit. Multivariate analysis confirmed lack of palliative care involvement and better performance status as independent factors for TLCD less than 60 days. Survival analyses showed that patients with palliative care involvement and those dying under palliative care service were likely to have significantly longer TLCD. Conclusions: Cancer patients who have no involvement of palliative care team in their management tend to receive chemotherapy near the EoL, have more aggressive EoL care, and have higher risk of dying die from treatment related complications. Palliative care should be involved early in the care of cancer patients.

Chemotherapy for small cell lung cancer: a comprehensive review

Combination chemotherapy is the current strategy of choice for treatment of small cell lung cancer (SCLC). Platinum containing combination regimens are superior to non-platinum regimens in limited stage-SCLC and possibly also in extensive stage-SCLC as first and second-line treatments. The addition of ifosfamide to platinum containing regimens may improve the outcome but at the price of increased toxicity. Suboptimal doses of chemotherapy result in inferior survival. Early intensified, accelerated and high-dose chemotherapy gave conflicting results and is not considered a standard option outside of clinical trials. A number of newer agents have provided promising results when used in combination regimens, for example, gemcitabine, irinotecan and topotecan. However, more studies are required to appropriately evaluate them. There is a definitive role for radiotherapy in LD-SCLC. However, timing and schedule are subject to further research. Novel approaches are currently being investigated in the hope of improving outcome.