Practical recommendation for rash and diarrhea management in Indian patients treated with tyrosine kinase inhibitors for the treatment of non‑small cell lung cancer.

Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro‑intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular‑guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR). The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs). Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient’s quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment. These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient’s quality of life and maintain compliance; however if these adverse events (AEs) are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non‑Small Cell Lung Cancer (NSCLC) patients receiving TKIs.

Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.

CONTEXT: Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies. AIMS: To determine the safety, doselimiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD). SETTINGS AND DESIGN: Phase 1, open-label, dose-escalation study in men and women ≥18 years of age. MATERIALS AND METHODS: An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD). STATISTICAL ANALYSIS USED: All data summaries were descriptive. PK parameters were estimated using compartmental analysis. RESULTS: 25 patients (16 male, 9 female, 26- 66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days. CONCLUSIONS: 2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.

Management of primary and metastatic triple negative breast cancer: Perceptions of oncologists from India.

Background: In order to document the understanding of current evidence for the management of triple negative breast cancer and application of this knowledge in daily practice, we conducted an interactive survey of practicing Indian oncologists. Materials and Methods: A core group of academic oncologists devised two hypothetical triple negative cases (metastatic and early breast cancer, respectively) and multiple choice options under different clinical circumstances. The respondents were practicing oncologists in different Indian cities who participated in either an online survey or a meeting. The participants electronically chose their preferred option based on their everyday practice. Results: A total of 152 oncologists participated. Just over half (53.8%) preferred taxane based chemotherapy as first-line chemotherapy in the metastatic setting. In the adjuvant setting, a taxane regimen was chosen by 61%. Over half of respondents (52.6%) underestimated the baseline survival of a patient with node positive triple-negative tumor and 18.9% overestimated this survival compared to the estimate of the Adjuvant! program. Discussion: This data offers insight into the perceptions and practice of a diverse cross-section of practicing oncologists in India with respect to their therapeutic choices in metastatic and adjuvant settings in triple negative breast cancer.

Haematologic paraneoplastic syndromes in pleural mesothelioma: A report of two cases and review of the literature.

Paraneoplastic syndromes are common in mesotheliomas but there is no report from India. Two cases of pleural mesothelioma with paraneoplastic haematologic syndromes, one with neutrophilic leukemoid reaction and the other with thrombocytosis, are presented in this report.

Isolated intraorbital metastasis in breast carcinoma.

We report a case of metastases to the eye, in a 30 year old lady with carcinoma breast leading to isolated metastatic involvement of the lateral rectus muscle with no evidence of metastases at any other site in the body after a follow up of one year after completion of chemotherapy.

A phase II study of gemcitabine and cisplatin in patients with advanced hepatocellular carcinoma.

The primary objective of this study was to determine the response rates of a combination of gemcitabine and cisplatin in unresectable hepatocellular carcinoma (HCC) in Indian patients. The secondary objectives were to evaluate the toxicity, time to progressive disease and overall survival for this combination. Chemonaive patients with histopathologically proven, bidimensionally measurable, stage Ill or IV unresectable HCC were enrolled into this study. All the patients were required to have a Zubrod's performance status not greater than 2, should not have undergone prior radiotherapy and were required to have adequate major organ function. Patients received gemcitabine (1250 mg/m2 intravenously over 30 to 60 min) on days 1 and 8, and cisplatin (70 mg/m2 intravenously over 2 hours) on day land every 21 days. Response assessment was done by a Computed Tomography scan after every two cycles of chemotherapy. From May to December 1999, 30 patients were enrolled in the study; they were all eligible for efficacy and toxicity analysis. Six (20%) patients achieved a partial response and 13 (43%) patients demonstrated stable disease with 11 (37%) patients showing disease progression. The median time to progression was 18 weeks (range 1 to 74 weeks) and the median duration of response was 13 weeks (range 4 to 68 weeks). The 1-year survival rate was 27% and the median overall survival was 21 weeks (95% CI: 17 to 43 weeks). WHO grade 3 and 4 anemia was seen in 11 (37%) and 2 (7%) patients, respectively. Four (13%) patients each experienced grade 3 and 4 neutropenia and grade 3 and 4 thrombocytopenia was seen in 2 (7%) patients each. Major, non-hematologic toxicities were grade 4 elevated bilirubin levels and grade 3 oral toxicity, in 1 patient (3%) each. This regimen was well tolerated and did show activity in Indian patients with advanced unresectable HCC. There is a need to further evaluate this combination in order to define its role in the treatment of HCC.

Trichosporon asahii as an emerging etiologic agent of disseminated trichosporonosis: A case report and an update.

PURPOSE: To report a fatal case of disseminated trichosporonosis caused by Trichosporon asahii in a patient with acute myeloblastic leukemia (AML) and to present an update on systemic trichosporonosis with special reference to India. METHODS: The diagnosis was based on repeated demonstration of budding yeast cells and arthroconidia by direct microscopic examination of sputum and by isolation of T. asahii in culture of sputum and blood. The update is largely based upon literature search in Medline and Review of Medical and Veterinary Mycology. RESULTS: A 41-year-old male presented with acute myeloblastic leukemia, cough and fever. He had received cytotoxic drug therapy, broad spectrum antibiotics and was neutropenic. Trichosporon asahii was repeatedly demonstrated in his sputum by direct microscopy and culture, and also isolated from blood. It was identified by appropriate morphological and physiological characteristics viz., arthroconidium formation, diazonium blue B reaction, urease activity and assimilation of carbon and nitrogen compounds. The identification was confirmed by PCR amplification and direct DNA sequencing of internally transcribed spacer (ITS) 1 and ITS2 of rDNA. CONCLUSION: With greater awareness of etiologic significance of T.asahii, trichosporonosis is likely to be recognised more frequently than apparent from the available published reports.

Small cell carcinoma of the gall bladder: case report and review of literature.

Small cell carcinoma of the gall bladder is a very rare tumor. The neoplasm is highly lethal, metastasizes early, and may cause death shortly after diagnosis. Here we report a 56 year old male with small cell carcinoma of the gall bladder metastatic to the liver. He attained partial remission with 5 fluouracil, cisplatin based chemotherapy. However, the disease progressed after 3 months and salvage chemotherapy with docetaxel and caboplatin failed to produce any tumour response. He succumbed to the illness 13 months after cholecystectomy.

Ewing's sarcoma with central nervous system metastasis--report of two cases.

Isolated central nervous metastasis is rare in patients with Ewing's sarcoma. Here we report two cases with CNS metastasis as the sole manifestation of relapse with a brief review of the literature.

Cardiac metastasis from carcinoma breast--a case report.

Secondary neoplasms of the heart are more common than primary tumours. Metastasis occurs most commonly from bronchogenic carcinoma followed by lymphoma and carcinoma breast. Most often cardiac metastasis go undetected as they are asymptomatic and occurs as a terminal event. A 51 year old lady who developed cardiac metastasis from carcinoma breast diagnosed during life is reported with brief review of the literature.

Pre leukemic granulocytic sarcoma of vagina. A case report with review of literature.

Granulocytic sarcoma is an extramedullary tumor of malignant granulocytic progenitor cells, that may precede the onset of acute myeloid leukemia or appear during the leukemic manifestation or blastic crisis of chronic myeloproliferative disorders. We describe a case of granulocytic sarcoma of vagina in a 27 year old woman treated with local radiotherapy. After seven months of follow up she developed acute myeloid leukemia. The case has been presented in view of its rarity and discussed in light of the available literature.

Extrapolated response dose as a potential tool in radiotherapy and chemo-radiotherapy of head and neck cancers.

An analysis of head and neck cancer patients treated by radiotherapy (RT) alone (114 patients) and by chemo-radiotherapy (RT + CT) (115 patients) was carried out; the doses varied from 40-77 Gy and 35-71 Gy in RT and RT + CT groups respectively. The chemotherapy (CT) (induction/concurrent) drugs used were 5-FU, cisplatin, methotrexate either single or in combination. Extrapolated response dose values were evaluated with alpha/beta values of 10, 2.5 and 6 Gy for acute, late complications and tumour response, respectively. Dose enhancement factor (DEF) and Therapeutic gain factor (TGF) values were evaluated on the basis of ERD for patients receiving 5-FU RTCT (72 patients). ERD vs late complication rate and response rate curves were drawn for RT, RT + CT (< 7 cycles), RT + CT (> 6 cycles) and RT + CT (cumulative). DEF values for response rate were 0.95, 0.95 and 0.82 for the three RT + CT groups respectively. Similarly DEF values for late complication rate were evaluated as 0.87, 0.93 and 0.88. TGF values for RT + CT were 1.09, 1.02 and 0.93. TGF values indicated lack of significant influence of CT on clinical outcome. The correlation of ERD with late complication, response and status at last follow up (NED) was statistically significant for both groups (P < 0.01). ERD did not correlated with acute complication in RT group (P > 0.01). From the present analysis, in RT + CT treatments of head and neck cancers, an ERD value of 69 Gy is suggested as the limit for an acceptable 5% late complication rate.

Hepatocellular carcinoma metastatic to bones (Case report with review of literature).

A seventy year old man presented with bone pains. Investigation revealed a metastatic bone lesion in the humerus. The primary was found in the liver. The patient achieved good palliation with chemotherapy and radiotherapy and survived for one year.