Development of low dose immunotherapy

Conceptualised by Professor Kumar Prabhash and I. Immunotherapy regimens for treatment of advanced head and neck cancer are accessible to only 1%-3% patients because of their high cost. Hence developed a low dose dose immunotherapy regimen. This low dose regimen improves outcomes and quality of life. In addition, this brought the treatment cost down from 60-70 lakhs per year to below 5.0 lakhs per year. We performed the first-ever randomized study to demonstrate that addition of low dose nivolumab to OMCT improved survival and is an alternative standard of care for those who cannot access full-dose.

Key takeaway: Immunotherapy is accesible to only 1-3% of patients due to high cost. We conceptualised and proved that a novel low-dose regimen is also effective while bringing down costs by greater than 90%.

Development of double metronomic chemotherapy

This work was performed by me, in collaboration with Professor Kumar Prabhash and Professor Shripad Banavali. We identified in 2010, that the head and neck cancer palliative systemic therapy regimen of choice, the EXTREME regimen (per month cost used to be 3.5-4.0 lakhs) was unaffordable to greater than 90% of our patients. In addition, this regimen was intravenous hence requiring frequent hospital visits. It led to severe side effects in 82% of patients. Hence the majority of head and neck cancer patients were unable to take this regimen. Hence, we started using an oral metronomic combination therapy of methotrexate and celecoxib. This regimen was oral, had good results and used to cost about 1000 rupees per month. The initial cohort studies of 18 and 64 patients were published in the Indian journal of cancer and clinical oncology journal. Subsequently, using this data, we ran a randomized phase 2 study of 110 patients (2011-2013) in which this metronomic regimen was compared against the intravenous chemotherapy regimen. This phase 2 randomized study showed that the oral double metronomic regimen of methotrexate and celecoxib was better than the IV standard cisplatin regimen both in terms of better outcomes and fewer side effects. With these encouraging results, we performed a phase 3 study (2015-2020) comparing the low-cost metronomic regimen against the intravenous cisplatin regimen in 400 plus patients. This study proved beyond doubt that the oral metronomic regimen is better tolerated, has better outcomes and also leads to improvement in quality of life. This study was published in Lancet Global health and now this oral, low-cost regimen is considered one of the standard regimens and has entered practice guidelines.

Key takeaway: Existing palliative treatment of choice was unaffordable to 90% of patients with advanced head and neck cancer and caused distressing side effects in 82% and required hospital access for IV administration. We developed a regimen that’s very cheap, given orally and was proven to be more effective and with fewer side effects than the previous treatment of choice.

Development of triple metronomic chemotherapy-

This work was performed by me, in collaboration with Professor Kumar Prabhash, Professor Manoj Mahimkar, Dr Atanu Bhattacharjee, Professor Vikram Gota and Professor Shripad Banavali. We identified that double metronomic chemotherapy, docetaxel, cabazitaxel, though useful, was not working in platinum-refractory head and neck cancers ie, patients who fail after receiving cisplatin. So, we decided to biologically model it. However, there were no effective statistical models available for biologically modelling of this regimen as most chemotherapies are doses with the concept of maximum tolerable dose. So traditional phase 1 studies looked at adverse events as a criterion for the selection of dose. However, in metronomic dosing, the doses used are low and hence these traditional phase 1 models would fail. Hence, we made an innovative model where we would track the decline in circulating endothelial cells from baseline at day 8 and decrease in size of the tumour on radiological scans. Using this model, we made the first-ever phase ½ study of metronomic dosing. This biologically effective dose led to incredibly high response rates, improvement in quality of life and outcomes similar to that of immunotherapy drugs. These results were published in the Journal of clinical oncology (impact factor-44.5), one of the highest impact factor journals in oncology. The difference was immunotherapy drugs (Nivolumab or Pembrolizumab) for 1-month treatment cost 3-4 lakhs while this treatment cost 2000 rupees only.

Key takeaway: Conceptualized and developed an alternative regimen to immunotherapy in a specific subset of patients (platinum-refractory head and neck cancer) which proved similarly effective and tolerated as immunotherapy at under 1% of its cost.

Development of 3 weekly cisplatin in head and neck cancer

This work was performed in collaboration with Professor Kumar Prabhash, Professor Vanita Noronha, and Professor Shripad Banavali. It was an age-old question that which schedule of cisplatin (weekly or 3 weekly) along with radiation is the best. The answer was provided in this study which was a phase 3, randomised first-ever study answering this question. The results were published in the Journal of clinical oncology, one of the highest impact factor journals in oncology.

Key takeaway: Provided robust, treatment-affecting data on the optimal regimen for cisplatin usage concomitant to radiation in head and neck cancer.

Development of docetaxel in cisplatin ineligible head and neck cancer

This work was performed in collaboration with Professor Kumar Prabhash. There was no standard of care treatment to be given with radiation in cisplatin ineligible patients. Docetaxel as radiosensitizer was conceptualized and a large phase 3 study was done. This study proved that Docetaxel improved outcomes over radiation alone. This indeed improved outcomes and the results were presented at ASCO 2022 meeting.

Key takeaway: Provided robust data to prove efficacy of drug docetaxel when added to radiation in cisplatin ineligible head and neck cancers.

Development of neoadjuvant chemotherapy for organ preservation in oral cancer

This work was performed in collaboration with Professor Kumar Prabhash and Professor Devendra Chaukar. In surgery for oral cancer, often the mandible has to be cut, Hence, we designed a strategy whereby giving neoadjuvant chemotherapy will lead to a shrinkage of the tumor and hence surgery would be done with preservation of the mandible. Preservation of the mandible leads to better cosmesis, better Qol and better oral functions. Hence this was an important study. We did a randomised study and the long-term outcomes proved that the mandible can be preserved without impact on cancer-related outcomes. That is preservation of the mandible after NACT does not lead to an early recurrence of cancer. This randomised study was published in the Journal of clinical oncology , one of the highest impact factor journals in oncology.

Key takeaway: Conceptualised giving a kind of chemotherapy (neoadjuvant chemotherapy) which led to shrinkage of jaw tumours to the point where they could be surgically removed without having to remove the jaw and thus preserving it for the patient.

Development of neoadjuvant chemotherapy for borderline resectable cancers

In India 80-85% of patients present in a locally advanced stage. In many instances, the cancer is so advanced that surgery is not possible. If treated with radiation then most patients die within 1 year. Hence, we developed a strategy of treating these patients with neoadjuvant chemotherapy. Once tumor shrink post neoadjuvant therapy we would operate on them. This strategy led to a prolongation of life.

Key takeaway: Head and neck cancers are often advanced when they are first seen by doctors and hence surgery is not possible on them. We showed that by giving neoadjuvant chemotherapy, these advanced tumours could be shrunk down enough for them to be operated upon hence prolonging patients’ lifespan.

Development of systemic therapy in Thyroid Cancer

Dr Vijay Patil has experience of treating multiple systemic therapies including targeted therapies, sorafenib, lenvatinib, cabozantinib, vandetanib , RET inhibitors, B-RAF inhibitors and immunotherapy.

Salivary gland tumors

Dr Vijay Patil has experience of treating with multiple systemic therapies including targeted therapies, axitinib, TDM-1, Trastuzumab, Trastuzumab-Pertuzumab, sorafenib, lenvatinib, cabozantinib, vandetanib , RET inhibitors, B-RAF inhibitors and immunotherapy.

Skull base tumors

Dr Vijay Patil has experience of treating with multiple systemic therapies including targeted therapies and immunotherapies. He developed the neoadjuvant regimen of Cisplatin & etoposide in sinonasal malignancies.

NUT midline carcinomas

Dr Vijay Patil has experience of treating with multiple systemic therapies including targeted therapies and immunotherapies.