No abstract

Imatinib mesylate, a signal transduction inhibitor molecule, has been introduced in the treatment of chronic myelogenous leukemia (CML) since May 2001. By its unique mechanism of action, the drug has revolutionized the management of chronic phase CML. The drug is generally well tolerated. A number of hematological and non-hematological side-effects have been reported. Fatal bone marrow (BM) aplasia has rarely been reported. A 46-year-old women with chronic phase CML was treated with imatinib. Six weeks later she developed severe pancytopenia associated with fever, chest infection and bleeding. A BM biopsy revealed hypoplasia (BM cellularity < 5%). She died of pulmonary mucormycosis. CML patients on imatinib therapy need close monitoring. Those pre-treated with busulfan and interferon-alpha may be at a higher risk of developing BM aplasia.

Metastases to central nervous system (CNS) are very common in nonsmall cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-positive mutation. Brain is the most affected part of CNS where blood-brain barrier (BBB) presents a challenge to currently available chemotherapeutic agents as well as first- (erlotinib and gefitinib) and second (afatinib)-generation EGFR tyrosine kinase inhibitors (TKIs) due to their poor penetrability. A rapid development of EGFR T790M secondary mutation is another cause of treatment failure, and patients tend to progress despite initial response to first- and second-generation EGFR TKIs. Moreover, conventional treatments with heavy dose of radiation have a number of side effects compared to benefits attained. Recently, third-generation EGFR TKIs have been developed with proven efficacy in various clinical setups against EGFR mutation-positive cases of brain metastases in NSCLC. One such agent, osimertinib, is available in India. It has not only better penetration ability to BBB compared to other EGFR TKIs but also has significantly increased potency for most prevalent EGFR T790M mutations. Furthermore, it is active in patients who progress upon first- and second-generation EGFR TKIs. The purpose of this review article is to present an updated clinical preview of EGFR TKIs over conventional treatment, mainly radiation therapy to consider them as "use first" agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC.

BACKGROUND: Unresectable and metastatic gastric cancers carry a poor and dismal prognosis. Several phase II

PurposeAdherence to international antiemetic prophylaxis guidelines like those of ASCO can result in better control of chemotherapy-induced nausea and vomiting; however, the extent of implementation of such guidelines in India is unknown. Therefore, this survey was planned.MethodsThis study was an anonymized cross-sectional survey approved by the ethics committee. Survey items were generated from the clinical questions given in the ASCO guidelines. The survey was disseminated through personal contacts at an oncology conference and via e-mail to various community oncology centers across India. The B1, B2, and B3 domains included questions regarding the optimal antiemetic prophylaxis for high, moderate, and low-minimal emetogenic regimens.ResultsSixty-six (62.9%) of 105 responded and 65 centers (98.5%) were aware of the published guidelines. The partial, full, and no implementation scores were 92.5%, 4.5%, and 3.0%, respectively. Full implementation was better for the low-minimal emetogenic regimens (34.8%) than the highly emetogenic regimens (6.1%). The three most frequent reasons for hampered implementation of ASCO guidelines in routine chemotherapy practice cited by centers were a lack of sensitization (26 centers; 39.4%), lack of national guidelines (12 centers; 18.2%), and lack of administrative support (10 centers; 15.2%).ConclusionAwareness regarding ASCO antiemetic guidelines is satisfactory in Indian oncology practices; however, there is a need for sensitization of oncologists toward complete implementation of these guidelines in their clinical practice.

Introduction: Anemia is a common, underestimated problem in cancer patients receiving myelosuppressive chemotherapy and has significant adverse effect on the quality of life and outcome. Darbepoetin has been shown to be effective in this setting, but controversy surrounds it actual use. Methods: We analyzed prospectively collected clinical practice data of patients receiving darbepoetin in a real-world setting for this retrospective audit. Patients with baseline hemoglobin (Hb) of <11 g/dl were included in this analysis. Their medical records were audited using a predetermined 35-point pro forma. Results: There were a total of 274 patients with advanced cancer receiving myelosuppressive chemotherapy who had baseline Hb <11 g/dl and who were given darbepoetin. Head-and-neck squamous cell carcinoma, lung cancer, and breast cancer were the most common cancers. Their median baseline Hb was 8.9 g/dl which rose to 11.2 g/dl at the end of commenced therapy, along with improved symptomatology. There were no new toxicities, and only two patients required discontinuation of darbepoetin due to toxicity. Conclusion: Darbepoetin is safe and effective in the prevention and management of anemia among patients receiving myelosuppressive chemotherapy.

This is a case report of a young adult presenting with hemorrhagic pleural effusion. Chest CT scan showed loculated pleural effusion with pleural nodule. Whole body PET scan showed thickening of pleura with multiple enhancing pleural nodules with different metabolic activity. Pleural nodule was biopsied which on histopathology showed pleural synovial sarcoma.

6596 Background: Imatinib Mesylate, a BCR-ABL tyrosine kinase inhibitor produces sustained complete hematological response (CHR) in CML patients in chronic phase. There is a paucity of information on the effects of imatinib on the bone marrow (BM) morphology and angiogenesis. We evaluated the sequential changes in these parameters in 22 CML chronic phase patients treated with first line imatinib (400 mg) and compared with 10 controls (non-hematological malignancies). Methods: Trephine BM biopsies were evaluated by means of morphology, morphometry, Gomori’s stain and CD 34 staining. Reticulin fibrosis was graded from grade 1 to grade 4. Microvessel density (MVD) was calculated by counting the microvessels in hot spots (400 ×). Final value was mean of 10 fields. Total vascular area (TVA) was calculated by image analysis and expressed as percentage of the total area. Results: 22 patients were included in the study. Median age was 34 years (range 20–58 years). All patients attained a CHR at a median of 18 days. Major cytogenetic response was seen in 64%, minor response in 27% and no response in 9% of patients. Baseline BM cellularity was increased in all patents as compared to controls. The median cellularity at 6 months and 1 year was decreased to 60% and 50% respectively. The median grade of reticulin fibrosis at baseline was grade 3 as compared to controls (median grade 1). There was a significant decrease in reticulin fibrosis at 6 months and 1 year (median-grade 1, p=0.04). The median MVD at baseline was 8.25 (range 6–26) and was increased as compared to controls (median MVD-3.6). There was a significant decrease in MVD at 6 months and 1 year (median MVD-4.0, p=0.04). Similarly the TVA decreased from 6.2% at baseline to 4.3% at 1 year. These changes correlated with the cytogenetic responses. Two patients who had disease progression during therapy showed reversal in the bone marrow changes. Conclusions: Imatinib Mesylate produces significant effects on bone marrow morphometry and angiogenesis in patients with CML in chronic phase. There is a consistent decrease in bone marrow cellularity, reticulin fibrosis and microvessel density during therapy. No significant financial relationships to disclose.