Efficacy of bisphosphonates and other bone-targeted agents in metastatic bone disease from solid tumors other than breast and prostate cancers.

Metastatic bone disease complicates the course of malignancy in a substantial proportion of patients with advanced cancer. Bisphosphonates are now widely used to improve skeleton-related outcomes of patients with metastatic cancer to the bone. Most studies evaluating the efficacy of bisphosphonates and other bone-targeted agents have been performed in patients with metastatic breast and prostate cancer. Only a few studies have evaluated the role of bisphosphonates in other tumor types involving the skeletal system. We present a review of the clinical literature focusing on the current and potential roles of bisphosphonates (particularly zoledronic acid) and newer bone-targeted therapies in patients with metastasis to bone arising from solid tumors other than breast and prostate cancer.

Is levoleucovorin an alternative to racemic leucovorin? A literature review.

PURPOSE: Our purpose is to perform a comprehensive literature review of the use of levoleucovorin in gastrointestinal malignancies and to assess whether levoleucovorin is a reasonable alternative to racemic leucovorin. DESIGN: This is an extensive literature review of levoleucovorin use in patients with gastrointestinal tract malignancies. Our review revealed 125 citations with abstracts in the English language, including 16 randomized, controlled trials; 40 case studies; and 69 nonrandomized, controlled trials that included 6 pharmacokinetic (PK)/pharmacodynamic studies with 1 population PK study. RESULTS: Upon our review, there were 2 randomized controlled trials that directly compared racemic leucovorin with levoleucovorin. Goldberg et al noted that there was no statistically significant difference between time to progression (P = .78) and time to death (P = .57). Furthermore, Scheithauer et al again noted no significant difference in terms of response rates (25% vs. 32%; P = .25), median survival time (15 months vs. 14.5 months; P = .28), overall survival at 1 year (58.3% vs. 60.6%; P = .72), and probability of survival at 2 years (15.3% vs. 23%; P = .16). In addition, multiple other studies, including randomized, controlled; nonrandomized, controlled; and case studies, demonstrate similar efficacy and tolerability between the use of racemic leucovorin or levoleucovorin as a modulator of 5-FU. CONCLUSION: In many studies of patients with gastrointestinal malignancies, levoleucovorin has been used interchangeably and solely for racemic leucovorin for 5-FU modulation. Our literature review demonstrates that levoleucovorin has similar efficacy and tolerability when compared with racemic leucovorin, whether used in combination with other chemotherapeutic agents or alone.

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 (χ2P < .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 (χ2P < .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.

Oral contraceptives, abortion and breast cancer risk: a case control study in Saudi Arabia.

BACKGROUND: Several studies have examined the relationship between oral contraceptive pill (OCP) use, abortions and breast cancer, with mixed results. Hormonal changes associated with OCP use and abortion may increase risk of breast cancer over time, but there is a lack of studies studying this association in Saudi Arabian women. MATERIALS AND METHODS: We thererfore conducted a case control study in 192 women (92 as cases and 100 as controls), aged 30 to 65, and collected information on variables including examples related to study objectives and those which may confound findings. The Chi square test was used to detect associations between various factors and risk of breast cancer. RESULTS: We found no evidence of interaction between history of abortion or frequency of abortion and breast cancer risk (Chi square=0.422, p =0.420 and 1, p =0.169) respectively. Oral contraceptives did not confer risk for breast cancer overall (OR=0.276, 95%CI 0.092-0.829, p=0.524), while long term use of OCP was associated with increased risk of breast cancer (OR=0.297, 95%CI 0.158-0.557, p=0.001), with higher association for those who used 10 years or more of OCPs (OR=0.282, 95%CI 0.095-0.835, p=0.02). Age at first use of OCPs had no effect on breast cancer risk (p=0.452) or age at diagnosis (p=0.074). CONCLUSIONS: Prolonged use of OC (more than 10 years) may be associated with increased risk of breast cancer in Saudi women. Larger population based studies are needed to confirm this finding in this population.

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.

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.

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.