Neoadjuvant chemotherapy ver 2.0

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

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

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

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

Neoadjuvant Chemotherapy vs Neoadjuvant Chemoradiotherapy
• Randomized trials compared neoadjuvant chemotherapy with neoadjuvant
chemoradiotherapy; included patients with adenocarcinoma
1. 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

Neoadjuvant Chemotherapy vs Neoadjuvant Chemoradiotherapy
2. 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)

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.

Neoadjuvant Chemotherapy and Surgery vs Surgery Alone
Four showed no survival benefit to
neoadjuvant chemotherapy and three did show a survival benefit with
neoadjuvant chemotherapy compared with esophagectomy alone

Neoadjuvant chemotherapy versus primary surgery in ovarian carcinoma
FIGO stage III and IV
Overall Survival OutcomeConclusion
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

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

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

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

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

Neoadjuvant chemotherapy ver 2.0

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