Addition of 3-day aprepitant to ondansetron and dexamethasone for prophylaxis of chemotherapy-induced nausea and vomiting among patients with diffuse large B cell lymphoma receiving 5-day cisplatin-based chemotherapy.

BACKGROUND: Neurokinin-1 receptor antagonists, such as aprepitant are currently emerging as powerful prophylactic agents for chemotherapy-induced nausea and vomiting (CINV). Therefore, it is important to adjust the anti-emetic regimens based on personal risk factors of the patient, duration of the chemotherapy regimen and cost-effectiveness. PURPOSE: To determine the efficacy of the 3-day aprepitant along with ondansetron and dexamethasone in controlling CINV in patients with large B cell lymphoma receiving multiday-cisplatin regimen chemotherapy. METHODS: This is a pilot prospective cross-over trial. Patients were allocated to either aprepitant 125mg on day 1 and 80mg on days 2 & 3 or placebo in the first 2 cycles, with crossover to the opposite treatment in the 3rd and 4th cycles. The primary end point was complete response (CR) of both acute (days 1-5) and delayed (days 6-8) CINV. CR means neither to develop emetic episodes nor to use rescue anti-emetics medication. RESULTS: Twelve of the 15 patients recruited for the study were fully evaluable and completed 4 cycles of ESHAP regimen with a total of 48 cycles given. In the cycles with aprepitant and those without the CR were 83.3% and 0% respectively (p<0.05). Patients receiving aprepitant in the first 2 cycles recorded less nausea in subsequent cycles that were given without aprepitant. This was not statistically significant. CONCLUSION: This triple anti-emetic regimen showed efficacy in controlling the multi-day cisplatin-induced nausea and vomiting. Further randomized controlled trials are needed to compare between 3-day and 7-day aprepitant for multi-day cisplatin regimens.

The KRAS StripAssay for detection of KRAS mutation in Egyptian patients with colorectal cancer (CRC): a pilot study.

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. PURPOSE: Detection of KRAS mutation in Egyptian colorectal cancer (CRC) patients by the KRAS StripAssay. METHODS: Examination of 20 colorectal cancer (CRC) patients is done to detect KRAS mutations by KRAS StripAssay. For the StripAssay, a mutant-enriched PCR was followed by hybridization to KRAS-specific probes bound to a nitrocellulose strip. RESULTS: Among 20 patients, KRAS mutations were identified in 80% of patients by the KRAS StripAssay. CONCLUSIONS: Our preliminary results suggest that KRAS StripAssay is an alternative to protocols currently in use for KRAS mutation detection.

Novel mutations of the nucleophosmin (NPM-1) gene in Egyptian patients with acute myeloid leukemia: a pilot study.

UNLABELLED: Mutations of the nucleophosmin (NPM-1) gene have been reported in 50-60% of acute myeloid leukemia (AML) patients with normal karyotype. This work was designed to study the prevalence and nature of NPM1 gene mutations in a group of Egyptian patients with AML to get an idea about the profile of NPM1 gene mutations in our society. In 45 previously untreated patients with de novo AML, peripheral blood and/or bone marrow samples from all patients were subjected to microscopic morphologic examination, cytochemical analysis, immunophenotyping and karyotyping. Patients with normal cytogenetic results were selected for molecular analysis of NPM1 exon 12 by PCR amplification followed by DNA sequencing of the amplified product. Twenty-one patients (46.7%) had abnormal karyotype: six cases with t(15;17), five cases with t(8;21), five cases had trisomy 8, two cases carrying inv(3) and three cases had monosomy 7. The remaining 24 patients (53.3%) had normal karyotype. These patients were then subjected to molecular analysis. Out of these 24 patients with normal karyotype, mutant NPM-1 was detected in 11 patients (45.8%) by DNA sequencing; 2 cases showed type A mutation, 2 cases were harboring [ins 1015-1019 (CACG)], with point mutation [1006C>G], while the remaining 7 cases showed heterozygous deletion of nt A [del 1178 (A)]. CONCLUSION: Two novel NPM1 gene mutations were detected among our study population of AML patients identified as: the insertion CACG associated with point mutation, deletion of one base, or associated with point mutation. NPM1 gene mutations may become a new tool for monitoring minimal residual disease in AML with normal karyotype. Whether these previously unreported NPM-1 mutations will confer the same better outcome as previously reported mutations is currently unknown and warrants a larger study. CONCLUSION: Two novel NPM1 gene mutations were detected among our study population of AML patients identified as: the insertion CACG associated with point mutation, deletion of one base, or associated with point mutation. NPM1 gene mutations may become a new tool for monitoring minimal residual disease in AML with normal karyotype. Whether these previously unreported NPM-1 mutations will confer the same better outcome as previously reported mutations is currently unknown and warrants a larger study.

Palliative fractionated radiotherapy for bone metastases clinical and biological assessment of single versus multiple fractions.

BACKGROUND: Radiotherapy is effective in controlling pain from bone metastases which is a direct result of bone resorption. The urine resorption marker DPD proved important in assessing effectiveness of palliative radiotherapy to bone metastases. There is still controversy about the optimum adopted fractionation regimen. The aim of this study is to compare single fraction 8Gy with the standard treatment course of 30Gy/10 fractions/ 2weeks and to a third regimen of 20Gy/5 fractions/ 1week regarding factors impacting on QoL in terms of improved pain, mobility, analgesia scores, PS. The decrease of urine DPD was included as an objective parameter of response. PATIENTS AND METHODS: A prospective phase lll controlled study of palliative radiotherapy was conducted on 60 patients with bone metastases from known primary sites divided into 3 groups each of 20 patients balanced in age, sex, and type of malignancy, to be treated with one of three RT regimens. Assessment was done before and 6 weeks after treatment completion according to an established scoring system. RESULTS: Pain and analgesia scores were improved in the group receiving 30Gy/10 fr. regimen (p = 0.002 = 0.003) with no significant improvement of mobility (p=0.16) or PS (p=0.08). Urine DPD was decreased in this group by 43% in 9/20 patients. The group receiving single fraction of 8 Gy showed a significant improvement of scores of pain (p=0.008), analgesia (p=0.01), mobility (p=0.001), PS (p=0.01) and decrease in urine DPD by 33% in 7/20 patients. The group receiving 20Gy/5 fr. protocol achieved improved scores of pain (p=0.002), analgesia (p=0.008), mobility (p=0.03), and a decrease of ,-DPD by 56% in13/20 patients which was significantly better than the group receiving single 8Gy fraction,(p=0.03). There was a trend towards an increased number of reirradiations in patients receiving single fraction 8Gy, though not significant, whereas reirradiation was significantly correlated with the high initial ,-DPD level within all groups. CONCLUSION: The 20Gy/5fr. regimen seems to be superior to both the standard 30Gy/10fr. and the single fraction 8Gy as it achieved significant improvement of three clinical criteria, pain, analgesia and mobility concomitantly with significant decrease in urine DPD. Urine resorption markers confer subjective evaluation of radiotherapy response in patients with bone metastases. The high initial ,-DPD level was significantly correlated with the need to reirradiation. Key Words: Fractionated radiotherapy , Bone metastases , Bone resorption markers.