Keechilat Pavithran

Comparison of acute toxicities of two chemotherapy schedules for head and neck cancers

BACKGROUND Chemo-radiotherapy has become the standard of care for loco-regionally advanced head and neck cancers. Platinum based regimens are the most effective. Although benefits are proven with chemo-radiation, acute toxicities are markedly increased. The dose and delivery schedules of Cisplatin have ranged from intermittent higher dose [100 mg/m2] every 3 weeks to low dose [6 mg/m2] daily administration. At present there is no data indicating which regimen is superior. PURPOSE To compare acute toxicities of two chemotherapy schedules for head and neck cancers. MATERIALS AND METHODS A total of 83 head and neck cancer patients treated with two schedules of concurrent chemo RT were analyzed, retrospectively, for treatment toxicity. In group A [51 patients], chemotherapy [CT] was administered on week 1, 4 and 7 [cisplatin 100 mg/m2] over a period of 2-3 days. In group B [32 patients], CT was delivered weekly [cisplatin 40 mg/m2]. Radiotherapy dose was 7000 cGy in 35 fractions for definitive concurrent chemo-radiation and 6600 cGy in 33 fractions for adjuvant treatment. RESULTS Group B patients had increased grade III skin and hematological toxicity, where as patients in group A had more pharyngeal toxicity. Treatment interruptions and percentage of weight loss were higher in group B. Weekly CT schedule had higher rate of severe mucositis, which was statistically significant on both univariate [P = 0.005] and multivariate [P = 0.007] analysis. CONCLUSIONS Three weekly CT is less toxic than weekly. Weekly CT can be made more acceptable by reducing the dose and using feeding tubes for nutrition.

Aplastic anemia complicating systemic lupus erythematosus – report of a case and review of the literature

Abstract. Aplastic anemia is a very unusual feature of systemic lupus erythematosus (SLE). A 32-year-old lady presented with generalized purpuric lesions and was diagnosed as having immune thrombocytopenic purpura. Fourteen months later, she developed progressive pancytopenia, arthritis of small joints, and oral ulcers. Investigations confirmed SLE with aplastic anemia. High-dose methylprednisolone therapy had been unsuccessful in controlling the pancytopenia. She had a progressive course and died due to septicemia. Even though pancytopenia is common in SLE, a bone marrow examination should be done in all cases of persistent pancytopenia to exclude bone marrow aplasia. This will help in tailoring the treatment with more aggressive immunosuppressants.

INCREASED PLATE AND OSTEOSYNTHESIS RELATED COMPLICATIONS ASSOCIATED WITH POSTOPERATIVE CONCURRENT CHEMORADIOTHERAPY IN ORAL CANCER

Plate osteosynthesis is a widely used technique in head and neck reconstructive surgery. The objective of this study was to determine whether postoperative chemoradiotherapy, which was recently introduced for high‐risk head and neck cancer, affects plate and osteosynthesis related complications.

Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases

UNLABELLED Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34(+)/CD38(-) stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. FROM THE CLINICAL EDITOR Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia.

Development and molecular characterization of polymeric micro-nanofibrous scaffold of a defined 3-D niche for in vitro chemosensitivity analysis against acute myeloid leukemia cells

Standard in vitro drug testing employs 2-D tissue culture plate systems to test anti-leukemic drugs against cell adhesion-mediated drug-resistant leukemic cells that harbor in 3-D bone marrow microenvironments. This drawback necessitates the fabrication of 3-D scaffolds that have cell adhesion-mediated drug-resistant properties similar to in vivo niches. We therefore aimed at exploiting the known property of polyurethane (PU)/poly-l-lactic acid (PLLA) in forming a micro-nanofibrous structure to fabricate unique, not presented before, as far as we are aware, 3-D micro-nanofibrous scaffold composites using a thermally induced phase separation technique. Among the different combinations of PU/PLLA composites generated, the unique PU/PLLA 60:40 composite displayed micro-nanofibrous morphology similar to decellularized bone marrow with increased protein and fibronectin adsorption. Culturing of acute myeloid leukemia (AML) KG1a cells in FN-coated PU/PLLA 60:40 shows increased cell adhesion and cell adhesion-mediated drug resistance to the drugs cytarabine and daunorubicin without changing the original CD34+/CD38−/CD33− phenotype for 168 hours compared to fibronectin tissue culture plate systems. Molecularly, as seen in vivo, increased chemoresistance is associated with the upregulation of anti-apoptotic Bcl2 and the cell cycle regulatory protein p27Kip1 leading to cell growth arrest. Abrogation of Bcl2 activity by the Bcl2-specific inhibitor ABT 737 led to cell death in the presence of both cytarabine and daunorubicin, demonstrating that the cell adhesion-mediated drug resistance induced by Bcl2 and p27Kip1 in the scaffold was similar to that seen in vivo. These results thus show the utility of a platform technology, wherein drug testing can be performed before administering to patients without the necessity for stromal cells.

Gemcitabine and cisplatin-based combination chemotherapy in advanced hepatocellular carcinoma: An Indian experience

Background: Gemcitabine, an anti-metabolite, has some activity in hepatocellular carcinoma (HCC) in terms of responses and median survival. Aims: To analyze our experience with the use of gemcitabine in combination with cisplatin in HCC with respect to response, toxicity and survival. Materials and Methods: We studied the records of patients of HCC treated from January 2000 to December 2005 with gemcitabine and cisplatin, and found 24 of them to be evaluable for response, toxicity and survival. Results: Of 24 patients receiving three or more cycles of chemotherapy, six (25%) had a partial response and an additional 12 (50%) had stable disease. The median overall survival (OS) was 7.5 months (95% confidence interval, 4.5–10.5 months) and 1-year survival was 18%. Grade 3 and 4 anemia, thrombocytopenia and neutropenia were observed in, respectively, 17, 17 and 33% patients. The most frequent non-hematologic toxicities were nausea and vomiting and peripheral neuropathy. Conclusion: We report a partial response rate of 25% with stable disease in an additional 50% to three or more cycles of chemotherapy with gemcitabine and cisplatin, with a median OS of 7.5 months (95% confidence interval, 4.5–10.5) and acceptable toxicity profile from our single-center retrospective study of 24 patients of HCC. We trust that, in HCC, gemcitabine is a good drug to be the foundation to build the chemotherapeutic or targeted agents’ combinations on.

The significance of the site of origin in primary peritoneal carcinosarcoma: case report and literature review.

Primary peritoneal carcinomas are rare, highly aggressive malignant neoplasms containing both sarcomatous and carcinomatous elements. Surgical debulking is the mainstay of treatment for primary peritoneal carcinomas. Systemic chemotherapy is advised in all cases because of the early spreading of these tumours. We report on a case of primary peritoneal carcinosarcoma occurring in a 22-year-old woman.

Chronic myeloid leukaemia in a man with myasthenia gravis treated by thymectomy

Abstract: Treatment‐related chronic myeloid leukaemia (CML) is a less commonly recognised entity. It differs from treatment‐related acute leukaemias in frequency, clinical course, and prognosis. Previously two cases of CML have been described following treatment of myasthenia gravis associated with thymoma treated by thymectomy. We report a 25‐yr‐old man with myasthenia gravis without thymoma who developed CML, 68 months after thymectomy. Cytogenetic study showed translocation (9,22)(q34;q11) with 10% showing double Ph chromosome. Reverse‐transcriptase polymerase chain reaction (RT‐PCR) of peripheral blood demonstrated the presence of p210BCR/ABL with b3a2 transcripts. He was treated with hydroxyurea, and still remained in the chronic phase during the last 6 months of follow up. His myasthenic symptoms remained stable.

Drop metastases to the spinal cord from infratentorial glioblastoma multiforme in post-temozolomide era

Drop metastases from glioblastoma multiforme (GBM) to the spinal cord are extremely rare in clinical practice. We report herewith multiple drop metastases to the cervical and thoracic spinal cord presenting as paraplegia in a patient treated initially with tumor resection followed by chemoradiation and later with temozolomide-.based adjuvant chemotherapy.

Multiple myeloma presenting as eosinophilic pleural effusion

An elderly man, with no comorbidity, presented with rapidly accumulating left pleural effusion. He also had generalized adenopathy. Pleural fluid cytology showed exudative pleural effusion with eosinophilia. Supraclavicular lymph node biopsy was reported as amyloid. On further investigation he was found to have kappa‐light chain multiple myeloma. The final diagnosis was eosinophilic pleural effusion in a patient with multiple myeloma.