Neoadjuvant Chemotherapy
Chemotherapy uses drugs to destroy cancer cells, stop their growth, or ameliorate symptoms. In neoadjuvant (also called preoperative or primary) chemotherapy, drug treatment takes place before surgical extraction of a tumor. This is in contrast with adjuvant chemotherapy, which is drug treatment after surgery. Oncologists administer neoadjuvant therapy with the objective of reducing tumor size. Reduction of tumor mass decreases the extent and invasiveness of a surgery and makes it easier for the surgeon to distinguish between normal and cancerous tissue. In tumors initially diagnosed as non-operable or of borderline respectability, shrinking of the cancerous lesion can enable surgery and allow for adequate clean margins. The neoadjuvant chemotherapy not only facilitates the procedure but can also improve postoperative recovery and the long-term outcome for the patient.
The choice of a systemic treatment, such as chemotherapy, also depends on the perceived risk of distant metastasis. Particularly in locally advanced tumors with high metastatic potential, neoadjuvant chemotherapy offers the possibility to treat both primary lesions and micrometastases at distant sites. Unfortunately, chemotherapy is associated with serious side effects which can aggravate the overall health status of patients. There is a risk that the chemotherapy will make the patient so much sicker, he or she becomes unfit for surgery. This is a risk that the supervising doctor must weigh.
Neoadjuvant chemotherapy is usually given for inoperable breast, colorectal and lung cancers1-4 and it is a treatment option for many other solid tumors. Systemic preoperative treatment is employed in breast-conserving surgery1, tumors with borderline resectability 2,5 and locally advanced cancers6. Recent review articles published in the Journal of Surgical Oncology and related clinical journals show that neoadjuvant chemotherapy is being evaluated in different settings of esophageal, gastric, pancreatic, prostate, soft-tissue sarcoma, ovarian and cervical cancers7-13. In some disease settings, the primary neoadjuvant treatment is radiotherapy and chemotherapy can be administered concurrently or in sequence with radiation, in chemoradiation regimens.
The administration of neoadjuvant chemotherapy is performed in cycles, with each cycle consisting of a treatment period followed by a resting phase. Chemotherapy agents can be given orally or intravenously during a variable number of cycles14-16. Response to chemotherapy and patient fitness are important criteria in determining patient eligibility for surgery17. In some patients, surgery can be performed only weeks after the last cycle of preoperative chemotherapy.
The long-term benefits of neoadjuvant therapy plus surgery compared with surgery alone are a source of debate. In gastric, esophageal and cervical cancers only modest survival improvements have been observed with unclear risk-benefit ratios18-20. Significant survival benefits have been established in breast21 and lung22,23 cancers. Translation of clinical trial results to medical practice can be complex and depends on many factors. For example, in breast cancer, preoperative chemotherapy is currently recommended in locally advanced tumors21,24; however, the best course of treatment for early stages of the disease is unclear25.
Induction Chemotherapy
So is induction chemotherapy the same as neoadjuvant chemotherapy? The difference lies in the intent of the doctors planning treatment. If the chemotherapy is the primary treatment, intended to be the only treatment, it is called induction chemotherapy. The word neoadjuvant applies only if there is subsequent treatment of a different modality. And some insist the word neoadjuvant should be used only if the subsequent treatment is surgery, while the words induction and inductive can still be employed if the subsequent treatment is chemotherapy.
If a chemotherapy course is given prior to surgery, that chemo is called neoadjuvant. If a chemotherapy course is given prior to radiotherapy, some purists insist that chemo should not be called neoadjuvant but induction. Others will use neoadjuvant in both cases.
Chemotherapy: Before or after surgery?
The scheduling of chemotherapy relative to the surgical intervention is an area of active research in many cancers. Despite potential benefits, neoadjuvant chemotherapy also has risks when compared to systemic treatment in the postoperative setting (adjuvant chemotherapy). For one thing, delaying surgery allows potential metastasis of the cancer and spread to other parts of the body – making the disease more intractable26. For breast cancer, analysis of several clinical trials has not found significant differences between the efficacy of chemotherapy given before or after surgery27. Recent results from large clinical trials show that adjuvant and neoadjuvant chemotherapy regimens result in similar survival outcomes, but breast-conservation rates are improved with neoadjuvant chemotherapy28.
In lung cancer, the scheduling of chemotherapy is a subject of debate29. Adjuvant or neoadjuvant? There is lack of conclusive evidence supporting either approach, leading many to think that a general solution to the question might not be found30. As with other cancers (including breast and colorectal), the research is focusing on the development of personalized strategies that take into account many prognostic factors31.
Bibliography:
Books
Michael C Perry, The Chemotherapy Source Book, Lippincott Williams & Wilkins; Fourth Edition edition (October 1, 2007).
B. Sevin, P. Knapstein, O. Kochli, R. Angioli, Multimodality Therapy in Gynecologic Oncology, Thieme Medical Publishers; 1st edition (January 15, 1996).
Web
Cancerhelp.org
MD Anderson Cancer Center
Medscape.com
http://cme.medscape.com/viewarticle/590020_2
References
1. Liu SV, Melstrom L, Yao K, et al: Neoadjuvant therapy for breast cancer. J Surg Oncol 101:283-91, 2010
2. Julien LA, Thorson AG: Current neoadjuvant strategies in rectal cancer. J Surg Oncol 101:321-6, 2010
3. Fathi AT, Brahmer JR: Chemotherapy for advanced stage non-small cell lung cancer. Semin Thorac Cardiovasc Surg 20:210-6, 2008
4. Balmanoukian A, Ettinger DS: Managing the patient with borderline resectable lung cancer. Oncology (Williston Park) 24:234-41, 2010
5. Browner I, Purtell M: Chemotherapy in the older patient with operable non-small cell lung cancer: neoadjuvant and adjuvant regimens. Thorac Surg Clin 19:377-89, 2009
6. Socinski MA, Veeramachaneni NK, Haithcock BE: The many controversies of stage IIIA/IIIB lung cancer. Oncology (Williston Park) 24:256, 259, 2010
7. Hyngstrom JR, Posner MC: Neoadjuvant strategies for the treatment of locally advanced esophageal cancer. J Surg Oncol 101:299-304, 2010
8. Mezhir JJ, Tang LH, Coit DG: Neoadjuvant therapy of locally advanced gastric cancer. J Surg Oncol 101:305-14, 2010
9. Morganti AG, Massaccesi M, La Torre G, et al: A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol 17:194-205, 2010
10. Schutz FA, Oh WK: Neoadjuvant and adjuvant therapies in prostate cancer. Urol Clin North Am 37:97-104, Table of Contents, 2010
11. Weinberg LE, Rodriguez G, Hurteau JA: The role of neoadjuvant chemotherapy in treating advanced epithelial ovarian cancer. J Surg Oncol 101:334-43, 2010
12. Reynoso D, Subbiah V, Trent JC, et al: Neoadjuvant treatment of soft-tissue sarcoma: a multimodality approach. J Surg Oncol 101:327-33, 2010
13. Mori T, Hosokawa K, Kinoshita Y, et al: Neoadjuvant chemotherapy with weekly carboplatin and paclitaxel for locally advanced cervical carcinoma. Int J Gynecol Cancer 18:85-9, 2008
14. National Cancer Institute: Adjuvant and Neoadjuvant Therapy for Breast Cancer, 2010
15. American Cancer Society: Chemotherapy, Detailed Guide: Breast Cancer, 2010
16. Cancer Research UK: Why plan chemotherapy, 2010
17. Buchholz TA, Hunt KK, Whitman GJ, et al: Neoadjuvant chemotherapy for breast carcinoma: multidisciplinary considerations of benefits and risks. Cancer 98:1150-60, 2003
18. Morabito A, Carillio G, Longo R: Systemic treatment of gastric cancer. Crit Rev Oncol Hematol 70:216-34, 2009
19. Raja SG, Salhiyyah K, Nagarajan K: Does neoadjuvant chemotherapy improve survival in patients with resectable thoracic oesophageal cancer? Interact Cardiovasc Thorac Surg 6:661-4, 2007
20. Rydzewska L, Tierney J, Vale CL, et al: Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer. Cochrane Database Syst Rev:CD007406, 2010
21. Minckwitz Gv: Principles of preoperative chemotherapy. Breast Cancer Online 7, 2004
22. Song WA, Zhou NK, Wang W, et al: Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials. J Thorac Oncol 5:510-6, 2010
23. Burdett S, Stewart LA, Rydzewska L: A systematic review and meta-analysis of the literature: chemotherapy and surgery versus surgery alone in non-small cell lung cancer. J Thorac Oncol 1:611-21, 2006
24. Kaufmann M, von Minckwitz G, Rody A: Preoperative (neoadjuvant) systemic treatment of breast cancer. Breast 14:576-81, 2005
25. Cuppone F, Bria E, Carlini P, et al: Taxanes as primary chemotherapy for early breast cancer: meta-analysis of randomized trials. Cancer 113:238-46, 2008
26. Sevin BU: Multimodality Therapy in Gynecologic Oncology (ed Rev edition), Thieme Medical Pub, 1996
27. Mauri D, Pavlidis N, Ioannidis JP: Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 97:188-94, 2005
28. Rastogi P, Anderson SJ, Bear HD, et al: Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol 26:778-85, 2008
29. Strauss GM: Adjuvant vs Neoadjuvant Chemotherapy in Resectable NSCLC: Is That the Real Question? Oncology (Williston Park) 23, 2010
30. Besse B, Le Chevalier T: Adjuvant or induction cisplatin-based chemotherapy for operable lung cancer. Oncology (Williston Park) 23:520-7, 2009
31. Overdevest JB, Theodorescu D, Lee JK: Utilizing the molecular gateway: the path to personalized cancer management. Clin Chem 55:684-97, 2009
[IM1]This is because the inflammation that is associated with tumor growth is alleviated.
[IM2]Healthy tissue surrounding tumor. Failure to use adequate clean margins has been associated with recurrence.
[IM3]Specifically, the theoretical advantages of neoadjuvant chemotherapy are related to the potential establishment of metastatic sites at microscopic level (micro metastases).
Micro-metastases cannot be detected by current diagnostic tools. In general metasases cannot be treated surgically. Therefore they can only be treated by systemic therapies.
Since micro-metastases cannot be detected, this specific argument is based on a prophylactic concept. Some question the value of considering a prophylactic measure in the evaluation of the use of toxic therapies.
[IM4]Non-small cell lung cancer
[IM5]eg, curative surgery
[IM6]epithelial
[IM7]fit patients
[IM8]normally a month for breast cancer if blood analyses show regular results after chemotherapy
[IM9]in come cases chemotherapy can be given before and after surgery.