Neoadjuvant chemotherapy ver 2.0

neoadjuvant chemotherapy

1. Neoadjuvant Chemotherapy

2. Cancer: A Huge Burden

3. Cancer Scenario in India Cancer prevalence in India is estimated to be around 2.5 million, with over 800,000 new cases occurring each year

4. Introduction Chemotherapy uses drugs to destroy cancer cells, stop their growth, or ameliorate symptoms. In neoadjuvant (also called preoperative or primary) chemotherapy, treatment is performed before surgical extraction of a tumor with the objective of reducing its size

5. Advantages of Neoadjuvant Chemotherapy Inoperable tumors can be downsized allowing a curative intervention Organ Preservation In locally advanced rectal, laryngeal, and breast cancer It provides the opportunity to monitor response during treatment and allows changing or discontinuing treatment in case of nonresponsiveness Even if an advantage by changing therapy has not yet been proven, toxicity of an ineffective treatment can be avoided Demonstration of treatment efficacy, conversely, motivates patients to continue therapy despite toxicities Improve long term survival 1. Simon P, Journal Of Oncology Volume 2013, 2. Scott, Journal Of Clinical Oncology, 2012 3. Darkaki , The American Journal Of Hematology/Oncology, 2014

6. Advantages of Neoadjuvant Chemotherapy Residual cancer burden (RCB) is a powerful prognostic marker, sometimes changing the initial prognostic profile in either way In neoadjuvant trials predictive markers, tumor biology, mechanisms of resistance, and new treatment approaches can be investigated more rapidly 1. Simon P, Journal Of Oncology Volume 2013, 2. Scott, Journal Of Clinical Oncology, 2012 3. Darkaki , The American Journal Of Hematology/Oncology, 2014

7. Neoadjuvant Chemotherapy vs Neoadjuvant Chemoradiotherapy Randomized trials compared neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy ; included patients with adenocarcinoma In the Australian trial, 75 patients were randomized to receive preoperative cisplatin and 5-FU or preoperative chemoradiotherapy with the same drugs with a lower dose of 5-FU Pathological response rate was higher in the chemoradiotherapy arm (31% vs 8%; P = .01) Median progression-free survival for the two groups was 14 and 26 months Median overall survival was 29 months vs 32 months for the chemoradiotherapy arm but it did not reach statistical significance ( P = .83) Khaldoun et al, Cancer Control. 2013;20(2):89-96. Patti, World J Gastroenterol 2010 August 14; 16(30): 3793-3803

8. Neoadjuvant Chemotherapy vs Neoadjuvant Chemoradiotherapy Preoperative Chemotherapy or Radiochemotherapy in Esophago -gastric Adenocarcinoma Trial (POET) 126 patients with gastroesophageal junction adenocarcinoma Randomly assigned to receive chemotherapy alone (cisplatin/5-FU/ leucovorin ) for 15 weeks vs 12 weeks of the same regimen followed by low-dose radiotherapy concurrent with cisplatin and etoposide pCR rate was significantly higher in the induction arm (16% vs 2%), with a nonsignificant trend toward a better 3-year survival rate as well (47% vs 28%; P = .07) Khaldoun et al, Cancer Control. 2013;20(2):89-96. Patti, World J Gastroenterol 2010 August 14; 16(30): 3793-3803

9. Neoadjuvant Chemotherapy versus Adjuvant Therapy Primary objective to show an advantage due to earlier systemic therapy was not met, but it has been shown that neoadjuvant chemotherapy is as effective as adjuvant chemotherapy Rate of breast conservation in operable disease can be increased, even if the risk of local recurrence might be slightly higher. 1. Simon P, Journal Of Oncology Volume 2013, 2. Scott, Journal Of Clinical Oncology, 2012 3. Darkaki , The American Journal Of Hematology/Oncology, 2014

10. Neoadjuvant Chemotherapy and Surgery vs Surgery Alone F our showed no survival benefit to neoadjuvant chemotherapy and three did show a survival benefit with neoadjuvant chemotherapy compared with esophagectomy alone Khaldoun et al, Cancer Control. 2013;20(2):89-96. Patti, World J Gastroenterol 2010 August 14; 16(30): 3793-3803

11. Neoadjuvant chemotherapy versus primary surgery in ovarian carcinoma FIGO stage III and IV Overall Survival Outcome Conclusion No statistical difference in median OS and PFS between the two treatment groups With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account respectability, age, histology, stage, and performance status

12. Downside of Neoadjuvant Chemotherapy Many neoadjuvant chemotherapy regimens are cumbersome, requiring a highly motivated patient For Example One neoadjuvant therapy regimen for rectal cancer calls for following steps Weekly 2-hour infusional chemotherapy for 6 weeks Followed by a pause of 2 weeks The regimen goes on with daily 5-day intravenous chemotherapy at the beginning of daily 5-week radiation Therapy Another 5-day chemotherapy during the last week of radiation There is a mandatory pause of up to 8 weeks before surgery, the definitive therapy, to allow maximal tumor shrinkage The duration of neoadjuvant therapy in this regimen adds up to about 6 months

13. Downside of Neoadjuvant Chemotherapy Unlike an immediate removal of the tumor, prolonged neoadjuvant therapy for resectable cancer can be physically, socially, and emotionally difficult for patients, especially those with gynecologic malignancy Delay of the definitive treatment Increase in treatment-related toxicities

14. For whom it can be recommended as an alternative to AST ? Most large randomized trials of NAC versus AST indicate that these therapies offer equivalent disease free and overall survival benefits For operable breast cancer, NAC can be considered as an alternative to AST For patients who are deemed appropriate candidates for mastectomy but who desire less extensive surgery (breast conservation surgery). Success rate 5-36 %. Also in patients who can technically have a lumpectomy first but whose physical appearance 1. Simon P, Journal Of Oncology Volume 2013, 2. Scott, Journal Of Clinical Oncology, 2012 3. Darkaki , The American Journal Of Hematology/Oncology, 2014

15. For whom it can be recommended as an alternative to AST ? May also be advisable in patients who have medical contraindications to surgery or if they simply wish to delay surgery i.e. pregnant patient diagnosed in second and third trimester. NAC offers an optimal test situation for evaluation of new compounds and detection of new biologic or molecular discriminants of either response or resistance pCR may be used as a surrogate for survival, less cumbersome than overall survival and less time consuming 1. Simon P, Journal Of Oncology Volume 2013, 2. Scott, Journal Of Clinical Oncology, 2012 3. Darkaki , The American Journal Of Hematology/Oncology, 2014