Vijay Patil

A prospective randomized phase II study comparing metronomic chemotherapy with chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or inoperable squamous cell carcinoma of head and neck.

BACKGROUND Cetuximab based treatment is the recommended chemotherapy for head and neck squamous cell cancers in the palliative setting. However, due to financial constraints, intravenous (IV) chemotherapy without cetuximab is commonly used in lesser developed countries. We believe that oral metronomic chemotherapy may be safer and more effective in this setting. METHODS We conducted an open label, superiority, parallel design, randomized phase II trial comparing oral MCT [daily celecoxib (200mg twice daily) and weekly methotrexate (15mg/m(2))] to intravenous single agent cisplatin (IP) (75mg/m(2)) given 3 weekly. Eligible patients had head and neck cancers requiring palliative chemotherapy with ECOG PS 0-2 and adequate organ functions who could not afford cetuximab. The primary end point was progression-free survival. RESULTS 110 Patients were recruited between July 2011 to May 2013, 57 randomized to the MCT arm and 53 to the IP arm. Patients in the MCT arm had significantly longer PFS (median 101 days, 95% CI: 58.2-143.7 days) compared to the IP arm (median 66 days, 95% CI; 55.8-76.1 days) (p=0.014). The overall survival (OS) was also increased significantly in the MCT arm (median 249 days, 95% CI: 222.5-275.5 days) compared to the IP arm (median 152 days, 95% CI: 104.2-199.8 days) (p=0.02). There were fewer grade 3/4 adverse effects with MCT, which was not significant. (18.9% vs. 31.4%, P=0.14). CONCLUSION Oral metronomic chemotherapy has significantly better PFS and OS than single agent platinum in the palliative setting.

Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers

BACKGROUND The median survival of technically unresectable oral-cavity cancers (T4a and T4b) with non surgical therapy is 2-12 months. We hypothesized that neoadjuvant chemotherapy (NACT) could reduce the tumour size and result in successful resection and ultimately improved outcomes. We present a retrospective analysis of consecutive patients who received NACT at our centre between January 2008 and August 2012. PATIENTS AND METHODS All patients with technically unresectable oral cancers were assessed in a multidisciplinary clinic and received 2 cycles of NACT. After 2 cycles, patients were reassessed and planned for either surgery with subsequent CTRT or nonsurgical therapy including CT-RT, RT or palliation. SPSS version 16 was used for analysis of locoregional control and overall survival (OS). Univariate and multivariate analysis was done for factors affecting the OS. RESULTS 721 patients with stage IV oral-cavity cancer received NACT. 310 patients (43%) had sufficient reduction in tumour size and underwent surgical resection. Of the remaining patients, 167 received chemoradiation, 3 radical radiation and 241 palliative treatment alone The locoregional control rate at 24 months was 20.6% for the overall cohort, 32% in patients undergoing surgery and 15% in patients undergoing non surgical treatment (p=0.0001). The median estimated OS in patients undergoing surgery was 19.6 months (95% CI, 9.59-25.21 months) and 8.16 months (95%, CI 7.57-8.76) in patients treated with non surgical treatment (p=0.0001). CONCLUSION In our analysis, NACT led to successful resection and improved overall survival in a significant proportion of technically unresectable oral-cancer patients.

Role of paclitaxel and platinum-based adjuvant chemotherapy in high-risk penile cancer

Aim: To study the efficacy and safety of paclitaxel and platinum doublet chemotherapy in penile cancer patients with high-risk features of local failure. Materials and Methods: Retrospective analysis was done of patients with 19 carcinoma of the penis who were offered adjuvant chemotherapy with paclitaxel and platinum combination. The data regarding the surgical details, high-risk features for which chemotherapy was offered, chemotherapy toxicity details (in accordance with CTCAE vs 3), failure pattern, and survival data were noted. SPSS version 16 was used for statistical analysis. Descriptive and Kaplan–Meier survival analysis was performed. Results: Median age of patients was 48 years. Fifteen patients received paclitaxel in combination with cisplatin and four received paclitaxel with carboplatin in view of their low serum creatinine clearance. The treatment was completed by 12 patients (63.2%). Of 79 planned cycles, 50 were taken. The treatment was well tolerated with grade 3-4 gastrointestinal toxicity was seen in 1 patient, grade 3 neurological toxicity in one and grade 5 neutropenia in one patient. Treatment related death occured in one patient. The median follow-up was 15.33 months and 6 loco-regional relapsed had taken place. The estimated median DFS was 16.2 months and the estimated median OS was not reached. The estimated DFS for treatment completed patients was 23.13 months as against 2.16 months for patients not completing treatment. Conclusion: The platinum and taxane doublet chemotherapy was found to be safe and effective.

The Importance of Brain Metastasis in EGFR Mutation Positive NSCLC Patients

Introduction. Brain metastasis is a poor prognostic marker in lung cancer. However it is not known whether amongst patients with EGFR mutation those with brain metastases have a worse outcome. Methods. We compared the survival outcomes between EGFR mutation positive patients with and without brain metastases. In this retrospective analysis of prospective database of all metastatic lung cancer patients at our centre between July 2009 and December 2012, patients were treated with either combination chemotherapy or oral TKI. All patients with brain metastases received whole brain radiation. Kaplan Meier method was used for survival analysis and compared using log rank test. Results. 101 patients with EGFR mutated, metastatic lung cancer were studied. Fourteen had brain metastases and 87 did not. The common EGFR mutations were exon 19 deletion (61.3%) and exon 21 L858R mutation (28.7%). Overall response was 64% in extracranial metastasis group as compared to 50% in brain metastasis group. There was a significant worsening of median OS in the patients with brain metastases (11.6 months) compared with only extracranial metastases (18.7 months), P = 0.029. Conclusion. Amongst patients with EGFR mutant NSCLC, the presence of brain metastases leads to a worse outcome as compared to patients with extracranial metastases alone.

Induction chemotherapy in technically unresectable locally advanced oral cavity cancers: Does it make a difference?

BACKGROUND Locally advanced and unresectable oral cavity cancers have a poor prognosis. Induction might be beneficial in this setting by reducing tumor bulk and allowing definitive surgery. AIM To analyze the impact of induction chemotherapy on locally advanced, technically unresectable oral cavity cancers. MATERIALS AND METHODS Retrospective analysis of patients with locally advanced oral cavity cancers, who were treated with neoadjuvant chemotherapy (NACT) during the period between June 2009 and December 2010. Data from a prospectively filled database were analyzed for information on patient characteristics, chemotherapy received, toxicity, response rates, local treatment offered, patterns of failure, and overall survival. The statistical analysis was performed with SPSS version 16. RESULTS 123 patients, with a median age of 42 years were analyzed. Buccal mucosa was the most common subsite (68.30%). Three drug regimen was utilized in 26 patients (21.10%) and the rest received two drug regimen. Resectability was achieved in 17 patients treated with 3 drug regimen (68.00%) and 36 patients receiving 2 drug regimen. Febrile neutropenia was seen in 3 patients (3.09%) receiving 2 drug regimen and in 9 patients (34.62%) receiving 3 drug regimen. The estimated median OS was not reached in patients who had clinical response and underwent surgery as opposed to 8 months in patients treated with non-surgical modality post NACT (P = 0.0001). CONCLUSION Induction chemotherapy was effective in converting technically unresectable oral cavity cancers to operable disease in approximately 40% of patients and was associated with significantly improved overall survival in comparison to nonsurgical treatment.

Is there a role of induction chemotherapy followed by resection in T4b oral cavity cancers

OBJECTIVE The objective of the following study is to investigate the efficacy and impact of induction chemotherapy in T4b oral cavity cancers. MATERIALS AND METHODS Its a retrospective analysis of prospectively collected data of T4b oral cavity cancer patients who were offered induction chemotherapy and then assessed for resectability at the end of 2 cycles of chemotherapy. Post-induction these patients either underwent surgical or non-surgical local intervention depending upon their response. These patients were then followed-up until either recurrence progression or death whichever was later. Statistical analysis was performed by SPSS version 16. Descriptive analysis was performed. Factors affecting achievement of resectability were sought by univariate and multivariate analysis. The impact of surgery on overall survival (OS) was studied using Kaplan Meier survival analysis with the use of log rank test. RESULTS A total of 110 patients received chemotherapy. Median age been 41.5 years (range 25-66 years). 21 (20%) of our patient received 3 drug regimen while the rest of our patients received 2 drug regimen. Partial response was achieved in 28 patients, stable disease in 49 patients and progression was noted in 23 patients. Resectability was achieved in 34 (30.9%) of 110 patients. The estimated median OS in patients who underwent surgery was 18.0 months (95% confidence interval [CI]: 13.6-22.46 months) and for those treated with non-surgical treatment was 6.5 months (95% CI: 5.6-7.4 months) (P = 0.0001). CONCLUSION Use of induction chemotherapy is safe and can achieve resectability in 30.9% of our T4b patients. In those patients undergoing resection have much better OS then those who underwent non-surgical local treatment.

Metronomic Therapy: Chemotherapy revisited

Cytotoxic antiproliferative chemotherapeutic agents are the mainstay of treatment in cancers. Chemotherapy is usually administered every 2-3 weeks. Along with acute toxicity and long-term effects of cumulative doses, this strategy potentially allows regrowth of the tumor in the interval period and leads to the emergence of resistant populations of tumor cells. Moreover, even with intense chemotherapy, the outcome is stagnating for most of the tumors. There has been recent interest in the use of chemotherapy in fractionated doses which is far below the maximum tolerated dose. This is called metronomic scheduling of chemotherapy. Here, we review the biology and evidence for metronomic chemotherapy.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

Induction Chemotherapy in Technically Unresectable Locally Advanced Carcinoma of Maxillary Sinus

Background. Locally advanced carcinoma of maxillary sinus has been historically reported to have poor prognosis. We evaluated the role of NACT in improving the outcome in these patients. Methods. 41 patients with locally advanced technically unresectable (stage IVa) or unresectable maxillary carcinoma (stage IVb) were treated with induction chemotherapy between 2008 and 2011. The demographic profile, response and toxicity of chemotherapy, definitive treatment received, progression free survival (PFS), and overall survival (OS) were analyzed. Univariate and multivariate analysis were performed to determine factors associated with PFS and OS. Results. The chemotherapy included two drugs (platinum and taxane) in 34 patients (82.9%) and three drugs (platinum, taxane, and 5 FU) in 7 (17.1%). There was no complete response seen in any of the patients, stable disease in 18 (43.9%), partial response in 16 (39%), and progression in 7 (17.1%) patients. After induction, the treatment planned included surgery in 12 (29.3%), CT-RT in 24 (58.5%), radical RT in 1 (2.4%), palliative RT in 1 (2.4%), and palliative chemotherapy in 3 (7.3%) patients. Overall, the median PFS was 10.0 months. The OS at 24 months and 36 months was 41% and 35%, respectively. Conclusion. In unresectable maxillary carcinoma, induction chemotherapy has clinically significant benefit with acceptable toxicity.

Is There a Limitation of RECIST Criteria in Prediction of Pathological Response, in Head and Neck Cancers, to Postinduction Chemotherapy?

This study studied the coorelation between radiological response to induction chemotherapy and acheivement of pCR or near pCR. It was a retrospective analysis in which all patients who received NACT from 2008 till april 2012 were subjected to inclusion criteria. Coorelation analysis was performed between CR + PR and acheivement of pCR or near pCR. Twenty four patients were identified.The primary site of tumor was oral cavity in 19 patients (79.2%), maxilla in 2 patients (4.2%), laryngopharynx in 2 patients (4.2%) and oropharynx in 1 patient (4.2%). The clinical stage was stage IVA in 16 patients ( 66.7%) and IVB in 8 patients (33.3%). The overall response rates ie a combination of CR and PR was seen in 11patients (45.8%). The pCR was seen in 15 patients (62.5%) and rest had near pCR. There was no linear coorelation between radiological size decrement and tumor response. On coorelation analysis the spearman correlation coefficent was −0.039 (P = 0.857). This suggest that presently used radiological response criterias for response assesment in head and neck cancers severly limit our ability to identify patients who would have pCR or near pCR.