V. Patil

Oral Metronomic Chemotherapy in Recurrent, Metastatic and Locally Advanced Head and Neck Cancers

Sir d The treatment options in patients with metastatic and relapsed head and neck cancers that are not amenable for local treatment are limited [1,2]. Many different combination chemotherapy regimens with platinum as one of the agent have been used in such situations. However, none of them was clearly superior to each other and overall survival was not statistically improved with respect to the increase in the number of agents used [1,2]. The use of cetuximab in combination with cisplatin and 5-fluorouracil led to an improvement in overall survival with respect to the cisplatin and 5-fluorouracil combination [3]. However, in resource-poor settings the use of this combination is limited. Low-dose methotrexate and cyclooxygenase-2 inhibitors have an anti-angiogenic effect in head and neck cancer cell lines [4,5]. We report the effectiveness and toxicity of a metronomic chemotherapy with these agents for palliative intent chemotherapy in head and neck cancers. Fiftyseven patients who received metronomic chemotherapy from August 2010 to August 2011 were included. The schedule used was capsule celecoxib 200 mg twice daily and tablet methotrexate 15 mg/m 2 weekly. The median age of the patients was 52 years (29e74). The performance status (PS) was Eastern Cooperative Oncology Group PS 1 in 45 patients (78.9%) and PS 2 in 12 patients (21.1%). The median treatment-free interval after the last treatment modality was 6 months (1e40 months). All patients had squamous cell carcinoma with the oral cavity being the primary in 28 patients (49.10%). Twelve patients had metastatic disease, 44 had locally advanced disease not amenable to locoregional therapy and one patient with a resectable tumour was unwilling for either surgery or radiotherapy despite repeated counselling. The major grade 3 and 4 toxicities (CTCAE version 4.02) were mucositis, anaemia and thrombocytopenia in three, one and one patients, respectively. There was a complete response in two patients (3.5%), a partial response in seven (12.3%), stable disease in 41 (71.9%) and progression in six patients (10.5%). The median progression-free survival was 153 days and overall survival was 186 days. Inpatients with an eventfree period below 6 months from the previous treatment the overall survival was 153 days; in patients with an eventfree period above 6 months it was 221 days (P ¼ 0.01). We conclude that metronomic chemotherapy is well-tolerated and has a potential role in the palliative treatment of head and neck cancer.

Weekly paclitaxel as metronomic palliative chemotherapy in small cell lung cancer

Background: Topotecan is the standard second line agent used in relapsed small cell lung cancer (SCLC). However, the erratic availability and the cost of the drug has been a prohibitive factor for its use in second-line setting in India. Paclitaxel has shown antitumor activity in heavily pretreated patients with SCLC. Hence, this audit was performed to study the efficacy of weekly paclitaxel as a form of metronomic therapy in the second-line setting in SCLC. Materials and Methods: Fifty-seven patients of relapsed SCLC who presented to the thoracic medical oncology unit of Tata Memorial Centre, Mumbai between January 2011 and December 2015 were selected for this analysis. Weekly paclitaxel at a dose of 80 mg/m 2 was administered until progression or development of intolerable side effects or patient refusal. Data regarding baseline demographics, previous treatment history, response rate, progression-free survival, overall survival (OS), and toxicity to weekly paclitaxel was extracted from a prospectively maintained database in the thoracic medical oncology unit and was analyzed using SPSS version 16 (IBM, New York, USA). Kaplan-Meier survival analysis was performed. Results: Median age of the cohort was 58 years (40-77 years). Etoposide with carboplatin was the regimen used in 40 patients (70.2%) whereas the remaining 17 patients received etoposide with cisplatin (29.8%). Eastern Cooperative Oncology Group performance status at relapse was 1 in 3 (5.3%), 2 in 49 (86.0%), and 3 in 5 (8.7%) patients. The response rate and clinical benefit rate were 9.1% (5 patients) and 52.7% (29 patients), respectively. Grade 3-4 toxicities were seen in 10.5% (6 patients). The median PFS was 145 days (95% confidence interval [CI]: 116.6-173.5 days) whereas the median OS was 168 days (95% CI: 112.5-223.5 days). Conclusion: Weekly paclitaxel as a second line agent in relapsed small cell cancer of the lung is a feasible and well-tolerated agent.

Comparison of paclitaxel-cetuximab chemotherapy versus metronomic chemotherapy consisting of methotrexate and celecoxib as palliative chemotherapy in head and neck cancers

BACKGROUND The present match pair analysis was planned to compare the efficacy of cetuximab-paclitaxel-based chemotherapy versus metronomic therapy. MATERIALS AND METHODS Sixty patients with metastatic/recurrent head and neck squamous cell cancer treated with weekly paclitaxel (80 mg/m2) and cetuximab were matched with sixty patients treated with oral metronomic chemotherapy consisting of methotrexate and celecoxib. The progression-free survival (PFS) and overall survival (OS) between the cohorts were compared using log-rank test. Cox proportional regression model was used to identify independent factors affecting PFS and OS. RESULTS The median OS was 191 days (95% confidence interval [CI]: 122.2-259.8 days) in metronomic cohort and 256 days (95% CI 177.0-334.9 days) in cetuximab cohort (hazard ratio: 0.58, 95% CI: 0.35-0.95, P = 0.031). On Cox proportional hazard model, Eastern Cooperative Oncology Group Performance Status (0-1 vs. 2) and therapy (cetuximab versus metronomic) had a statistically significant impact on OS. CONCLUSION Cetuximab-based chemotherapy leads to a significant improvement in OS in the match pair analysis in comparison to metronomic chemotherapy.

Long-term survival outcomes of technically unresectable carcinoma maxilla postinduction chemotherapy

South Asian Journal of Cancer ♦ Volume 7 ♦ Issue 3 ♦ July-September 2018 213 Tournigand C, et al. Use of chemotherapy near the end of life: What factors matter? Ann Oncol 2017;28:809-17. 35. Pollockquestions K. Is home always the best and preferred place of death? bmj. 2015;19. 36. Mack JW, Chen K, Boscoe FP, Gesten FC, Roohan PJ, Schymura MJ, et al. High intensity of end-of-life care among adolescent and young adult cancer patients in the New York state medicaid program. Med Care 2015;53:1018-26. 37. Paris J, Morrison RS. Evaluating the effects of inpatient palliative care consultations on subsequent hospice use and place of death in patients with advanced GI cancers. J Oncol Pract 2014;10:174-7.

Applying the QUARTZ Trial Results in Clinical Practice: Development of a Prognostic Model Predicting Poor Outcomes for Non-small Cell Lung Cancers with Brain Metastases

AIMS The role of whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancers (NSCLC) has been questioned. However, no reliable criteria exist to identify patients who do not benefit from WBRT. The objective of the current study was to develop a prognostic model to identify such patients whose survival matches that of the Quality of Life after Treatment for Brain Metastases (QUARTZ) study. MATERIALS AND METHODS Outcome data of patients with NSCLC with brain metastases undergoing WBRT enrolled in a prospective observational study in a tertiary cancer centre were used to develop a prognostic model. Baseline clinico-radiological factors were used for development of the model. The model was internally validated and calibration accuracy was checked for prediction of 70 day mortality. The generated prognostic model was presented as a nomogram. RESULTS The median overall survival of 140 patients enrolled in the study was 166 days (95% confidence interval 108-242 days). The prognostic model identified gender, Karnofsky performance status and epidermal growth factor receptor activating mutation status as significant factors influencing overall survival. The model showed a modest discriminative ability with an optimism-corrected C-index of 0.64. However, model calibration error did reveal a moderate degree of calibration error. The high-risk subgroup identified by the model had a median overall survival of 67 days (95% confidence interval 56-101 days), which was similar to that observed in the QUARTZ trial. CONCLUSION This prognostic model derived from traditional clinico-radiological features had a modest ability to identify patients with poor prognosis who may not benefit from WBRT. However, the high-risk subgroup identified using this prognostic model had a survival similar to that observed for patients in the QUARTZ trial.

EMERALD: Emergency visit audit of patients treated under medical oncology in a tertiary cancer center: Logical steps to decrease the burden

Background: We are a tertiary care cancer center and have approximately 1000–1500 emergency visits by cancer patients undergoing treatment under the adult medical oncology unit each month. However, due to the lack of a systematic audit, we are unable to plan steps toward the improvement in quality of emergency services, and hence the audit was planned. Methods: All emergency visits under the adult medical oncology department in the month of July 2015 were audited. The cause of visit, the demographic details, cancer details, and chemotherapy status were obtained from the electronic medical records. The emergency visits were classified as avoidable or unavoidable. Descriptive statistics were performed. Reasons for avoidable emergency visits were sought. Results: Out of 1199 visits, 1168 visits were classifiable. Six hundred and ninety-six visits were classified as unavoidable (59.6%, 95% CI: 56.7–62.4), 386 visits were classified as probably avoidable visit (33.0%, 95% CI: 30.4–35.8) whereas the remaining 86 (7.4%, 95% CI: 6.0–9.01) were classified as absolutely avoidable. Two hundred and ninety-seven visits happened on weekends (25.6%) and 138 visits converted into an inpatient admission (11.9%). The factors associated with avoidable visits were curative intention of treatment (odds ratio - 2.49), discontinued chemotherapy status (risk ratio [RR] - 8.28), and private category file status (RR – 1.89). Conclusion: A proportion of visits to emergency services can be curtailed. Approximately one-fourth of patients are seen on weekends, and only about one-tenth of patients get admitted.

ROS1 rearranged nonsmall cell lung cancer and crizotinib: An Indian experience

ROS1 rearrangement acts as a driver mutation in 1-2% of NSCLC. Crizotinib is approved in this situation both in treatment naïve and pre-treated patients. Here we report our experience with crizotinib in patients with advanced NSCLC harbouring ROS1 rearrangement. Eleven patients were included in our study. More than half of our patients had associated comorbidities and one fourth of them had a compromised performance status. Out of 11 patients, 5 of them were exposed to crizotinib .The response rates among crizotinib treated patients was 80%. With a median follow up of 9 months, median PFS and OS were 5.4 months and 8.5 months respectively for the entire population. Analyzing the outcomes separately , median PFS and OS was not reached for those who received crizotinib compared to median PFS of 2.5 months and median OS of 4.2 months in those who were not exposed to crizotinib. The difference was statistically significant. Estimated 1 year OS was 80% for those who received crizotinib compared to 18% for who did not receive crizotinib. In conclusion, crizotinib is effective with acceptable side effect profile in patients with ROS1 rearranged NSCLC in our population.

Epidermal growth factor receptor positive lung cancer: The nontrial scenario

PURPOSE The aim of this study was to report the median overall survival (OS) in epidermal growth factor receptor (EGFR) mutation-positive patients who were managed out of a clinical trial. METHODS Nonsmall cell lung cancer patients harboring activating EGFR mutations who were either ineligible or refused participation in a clinical trial were selected for this analysis. The reason for not participating in trial, staging, treatment, and outcome details were obtained from a prospective lung cancer database. The Kaplan-Meier method was used to estimate OS. Log-rank test and Cox proportion hazard model were used for univariate and multivariate analysis, respectively. RESULTS We included 225 patients in this analysis. The median age of the cohort was 56 years (range 29-85 years). A compromised Eastern Cooperative Oncology Group performance status (PS) of >2 was the major reason (83 patients, 36.9%) for ineligibility of patients in a clinical trial. The major reason provided by eligible patients for refusal to participate in a clinical trial was long distance of travel and inability to comply with the study-mandated follow-up visits (65 patients, 28.9%). The median OS in patients with PS 0-2 was 18.17 months (95% confidence interval [CI]: 15.6-20.8 months) and it was 12.1 months (95% CI: 9.0-15.2 months) in patients with PS 3-4 (hazard ratio - 0.579 [95% CI: 0.398-0.843] P = 0.004). CONCLUSION EGFR positive patients who were ineligible for a clinical trial due to poor PS had lower survival; however, patients with good PS treated off-trial had similar OS to that reported in multiple clinical trials.

Repeat biopsy in epidermal growth factor receptor mutation-positive nonsmall cell lung cancer: Feasibility, limitations, and clinical utility in Indian patients

INTRODUCTION The feasibility and success rate of repeat biopsy for epidermal growth factor receptor (EGFR) mutation-positive lung cancers that have progressed on tyrosine kinase inhibitors (TKIs) are varied and merits further assessment. MATERIALS AND METHODS EGFR mutation-positive lung cancers were offered repeat biopsy upon progression on TKIs. Two groups of patients, first one on a clinical trial and second one from a database, were included for analysis. The feasibility to perform a repeat biopsy was analyzed in the first group. Success rate of biopsy and tissue adequacy for molecular testing was analyzed in both groups. Descriptive statistics were used for analyzing the demography, EGFR mutation type, tissue adequacy, and molecular profile at repeat biopsy. Kolmogorov-Smirnov test was used to assess normality of data. Two sample t-tests were used for comparison of proportions. RESULTS The feasibility of undergoing repeat biopsy was 77% (95% confidence interval [CI] of 69.4%-83.5%) in the first group (114/148 patients). Feasibility was not analyzed in the second group of patients. Out of 196 patients who underwent a repeat biopsy, 154 patients (78.6%; 95% CI: 72.2%-84.1%) had tumor tissue adequate for performing molecular testing. 27/196 (13.8%) patients did not have any evidence of malignancy on repeat biopsy whereas 15/196 (7.6%) patients had scanty tissue on repeat biopsy prohibiting molecular testing. Six patients (3.06%; 95% CI: 1.1%-6.5%) had small cell transformation. T790M mutation was detected in 12 out of the 42 patients (28.6%; 95% CI: 15.7-44.6) in whom EGFR testing was performed on repeat biopsy specimen. CONCLUSION Repeat biopsy was able to provide adequate tissue acquisition in only two-thirds of the patients. Liquid biopsy represents an important tool to bridge this gap.

Rechallenge temozolomide in glioma: A case series from India

INTRODUCTION Temozolomide (TMZ) is an integral part of upfront treatment of high-grade gliomas. It is administered postsurgery as concurrent therapy with radiation and subsequently as adjuvant chemotherapy for 6-12 cycles. It is unknown whether rechallenge of salvage TMZ in previously treated high-grade glioma has any efficacy. MATERIAL AND METHODS Patients treated with salvage rechallenged TMZ between January 2015 and August 2016 were included for this retrospective analysis. SPSS version 20 was used for this analysis. Time to event analysis was performed using the Kaplan-Meier method. Progression-free survival (PFS) and overall survival (OS) were estimated. The maximum grade of toxicity was noted in accordance with CTCAE version 4.02. RESULTS A total of 23 patients were selected for analysis with the median age being 43 years (range: 26-69 years). The tumor histopathology at baseline was astrocytoma Grade 2 in 1 patient, oligodendroglioma Grade 2 in 3 patients, anaplastic astrocytoma in 7 patients, anaplastic oligodendroglioma in 2 patients, and glioblastoma in 10 patients. All of them had previously received TMZ. The median numbers of previous TMZ cycles received were 6 (4-18). The median time to failure postlast treatment was 24 months (5-72 months). The median number of cycles of rechallenged salvage TMZ administered was 6 cycles (range: 1-18). Grade 3-4 myelosuppression was seen in 3 patients (13.4%). The median PFS was 459 days (95% confidence interval: 212.1-705.9). The median OS was 25 months. Six-month OS and 1-year OS were 81.4% and 75.1%, respectively. CONCLUSION Rechallenge with TMZ in recurrent glioma that had previously responded to TMZ is associated with improvement in PFS and OS and has a sufficiently long disease-free interval.