A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

Epidemiology and outcomes of nasopharyngeal carcinoma: Experience from a regional cancer center in Southern India.

CONTEXT: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer with significant geographical variation. There are limited data on epidemiology and outcomes of NPC reported from Southern India. SETTINGS AND DESIGN: Retrospective analysis. MATERIALS AND METHODS: We analyzed our hospital data between January 2005 and December 2011 with NPC and analyzed their demographic parameters and outcomes with therapy. RESULTS: A total 143 cases of NPC were identified. Median age at presentation was 35 years with male predominance. Majority (84%) of the cases had the WHO Type 3 histology. Nodal metastasis at presentation was seen in 90% of the cases, majority being bilateral. Distant metastasis was seen in 16% of the cases, most commonly at bone, lung, and liver. Concurrent chemoradiation with weekly cisplatin was offered to 84.7% of localized disease while 80% of these also received adjuvant chemotherapy. Complete remission and partial remission were achieved in 66.1% and 15.2% of the cases, respectively. Weekly cisplatin was well tolerated with Grade 3-4 toxicity seen in 22% of cases. At a median follow-up of 20 months, 2-year progression-free survival and overall survival were 67.2% and 79.5%, respectively. STATISTICAL ANALYSIS USED: SPSS software version 20. CONCLUSION: NPC is a rare head and neck malignancy in Southern India, presenting with advanced stage and more propensity to distant metastasis. It has good outcomes to concurrent chemoradiation with weekly schedule of cisplatin being well-tolerated regime. Further prospective studies to test this schedule and other novel agents in this potentially curable malignancy are warranted.

Epidemiology and Outcomes with Platinum-Based Chemotherapy in Recurrent or Metastatic Carcinoma Cervix in a Developing Country: Experience from a Tertiary Oncology Centre in Southern India.

INTRODUCTION: Carcinoma cervix is the leading cause of cancer in Indian women. Recurrent/metastatic cervix is the most aggressive form of the disease. There is paucity of data in this setting in Indian women regarding outcomes with palliative chemotherapy. METHODS: We retrospectively analyzed hospital registry data between January 2013 and December 2014 for recurrent/metastatic carcinoma cervix patients who were planned for palliative chemotherapy and assessed their demographic parameters, response and survival outcomes with chemotherapy. RESULTS: We identified 165 cases of recurrent/metastatic carcinoma cervix. Median age at presentation was 48 years. Most common symptoms at presentation were bleeding or white discharge per vagina and lower abdominal pain. Majority of the patients were multiparous. Histologically squamous cell carcinoma was found most commonly (93.3%) with adenocarcinoma and adenosquamous carcinoma being exceedingly uncommon (3.63% each). 38% of patients were upfront metastatic while rest were recurrent disease. Most common sites of metastasis were retroperitoneal lymph nodes (21.21%), liver (11.51%), lung (9.69%), supraclavicular lymph nodes (8.48%) and bone (7.27%). After a median of 6 cycles of paclitaxel and carboplatin based chemotherapy, overall response rate (ORR) was 26.7% with 10.5% complete remission (CR) and 16.4% partial remission (PR) rates. Median progression free survival (PFS) was 6 months while median overall survival (OS) was 11 months. CONCLUSION: Recurrent/metastatic cervical carcinoma is an aggressive disease. Our patients showed an ORR of 26.7% to palliative chemotherapy with median PFS of 6 months and median OS of 11 months. Further research is required related to novel targeted agents and nonplatinum doublets.

Can the Use of Bone Marrow Parameters Improve the Efficacy of Risk Prediction Scores in Chronic Myeloid Leukemia in Imatinib Era?

INTRODUCTION: Many attempts have been made to develop risk prediction scores for chronic myeloid leukemia in chronic phase (CML-CP) to identify the subgroup with a poorer response to therapy to enable early intensification of treatment. Because the bone marrow (BM) provides a more sensitive reflection of the disease process, we hypothesized that using BM parameters in the Sokal and European Treatment and Outcome Study (EUTOS) risk scores could improve their efficacy in an imatinib-treated population. MATERIALS AND METHODS: We analyzed cases of CML-CP for their response and survival outcomes with imatinib using risk groupings determined by the Sokal and EUTOS scores using peripheral blood (PB) or BM parameters (Sokal-PB, Sokal-BM, EUTOS-PB, and EUTOS-BM). RESULTS: A total of 371 cases were analyzed. The concordance for risk groups was greater for the EUTOS scores (81.9%) than for the Sokal scores (68.1%) using PB versus BM parameters. For all 4 risk scores, the predictive efficacy was statistically significant. EUTOS-PB and EUTOS-BM could better prognosticate for progression-free survival (PFS) and overall survival (OS) between the low- and high-risk groups (P < .0001). However, with the Sokal risk score, the use of BM parameters improved the prognostic capacity for PFS between the low- and intermediate-risk groups, with a statistically significant difference (P = .025), but not for OS (P = .88). CONCLUSION: The use of BM parameters, a simple method that is feasible in routine clinical practice could improve the prognostic efficacy of the Sokal score for PFS but not for OS in low- and intermediate-risk groups. Further research to improve the sensitivity of risk scores for CML-CP prognosis and attempts at risk-directed therapy is warranted.

Prognostic significance of bone only metastasis compared to visceral metastasis in patients with carcinoma cervix treated with platinum-based chemotherapy.

CONTEXT: Carcinoma cervix is a leading cause of cancer in Indian females where 15%-60% of the cases eventually metastasize. Bone only metastasis is rare, and data on its response and survival with systemic therapy as compared to other visceral metastasis are limited. SETTINGS AND DESIGN: The study design was a retrospective analysis. MATERIALS AND METHODS: We retrospectively analyzed our data between May 2013 and April 2015 to identify the cases of bone only metastasis and visceral metastasis and tried to analyze their outcomes with paclitaxel- and carboplatin-based chemotherapy and bisphosphonates (for bone metastasis only). RESULTS: Totally, 12 cases with bone only metastasis (Group 1) and 43 cases with visceral metastasis (Group 2) were identified. Most common sites of bone metastasis were vertebrae (66.67%) and pelvis (25%) while that of visceral metastasis was liver (44.18%) and lung (34.88%). Only 33.33% and 34.88% of cases in Group 1 and Group 2, respectively, could complete all six cycles of chemotherapy. Overall, response rates were 41.67% and 30.32% in Group 1 and Group 2, respectively. Median progression-free survival and overall survival (OS) were 10 months and 14 months, respectively, in Group 1 as compared to 4 months and 9 months, respectively, in Group 2. The difference in survival was statistically significant. STATISTICAL ANALYSIS USED: It was carried out by SPSS software version 20. CONCLUSION: Bone only metastasis is a rare and distinct entity with favorable outcomes as compared to visceral metastasis. However, disease remains aggressive and poor OS emphasizing the need of further research.

Predictive and Prognostic Implications of Variant Philadelphia Translocations in CML: Experience From a Tertiary Oncology Center in Southern India.

INTRODUCTION: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by Philadelphia (Ph) chromosome with classical t(9;22)(q34;q11) seen in up to 90% of cases. However 5% to 10% of patients who present with variant Ph translocations (vPh) have been an area of research for their significance in predicting response to various therapies including tyrosine kinase inhibitors as well as prognosticating survival outcomes for many years involving varied patient populations, with conflicting results. MATERIALS AND METHODS: We retrospectively analyzed our data from January 2002 to December 2014. Patients with vPh in chronic phase of CML (CML-CP) were analyzed with respect to their demographic parameters, response to imatinib therapy, and survival and their data were compared with data of patients with classical Ph translocation (cPh). RESULTS: Of 615 patients diagnosed with CML-CP, 72 patients (11.7%) showed vPh. Most common chromosomes involved in these translocations were 14 (13.9%), 11 (12.5%), 19 (9.7%), and 7 (8.3%). Rates of complete hematological response, complete cytogenetic response, and major molecular response were not statistically different between the groups. At 5 years, event-free survival, failure-free survival, progression-free survival, and overall survival were 60% versus 67.9%, 62.7% versus 69.7%, 84.7% versus 92.1%, and 87.5% versus 92.4%, respectively, in vPh and cPh. The differences in survival were statistically not significant. CONCLUSION: To our knowledge, this is the largest series of variant translocations in CML-CP, pertaining to the Indian population. Our data suggest that the presence of vPh in CML has no significant effect in predicting response to imatinib as well as in prognosticating survival.

Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era-experience from a tertiary oncology centre in Southern India.

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. Over the years many prognostic models have been developed to better risk stratify this disease at baseline. Sokal, Euro, and EUTOS scores were developed in varied populations initially receiving various therapies. Here we try to identify their predictive and prognostic implication in a larger population of Indian patients with CML-CP (chronic phase) in the imatinib era.