Neoadjuvant chemotherapy

Neoadjuvant chemotherapy is appropriate for patients with locally advanced or inflammatory breast cancer, followed by local therapy and further adjuvant systemic therapy. 

The use of preoperative systemic therapy is gaining favor in both early-stage and locally advanced breast cancers. This approach to therapy, referred to as neoadjuvant or primary systemic therapy, most often consists of chemotherapy but in special circumstances also may include hormonal therapy (e.g., in inoperable patients with significant comorbidities). The advantages of preoperative systemic therapy include... 

Locally advanced breast cancer often is treated with neoadjuvant therapy to make the tumor surgically respectable. During neoadjuvant chemotherapy, laboratory values to monitor chemotherapy toxicity are obtained prior to each cycle of chemotherapy, and a physical examination and ultrasound exams to detect size of tumor are performed after the cycles of neoadjuvant therapy are completed. After a complete surgical resection, monitoring proceeds as described earlier for early breast cancer. 

List the rationale, advantages, disadvantages, and place in therapy for adjuvant and neoadjuvant chemotherapy... 

Another unique aspect of rectal cancer is the use of neoadjuvant therapy. Preoperative radiation with or without chemotherapy is given to downstage the tumor prior to surgical resection to improve sphincter preservation by making the surgical procedure easier to perform. The issue of preoperative versus postoperative radiation is a subject of debate and investigation in the United States and will require further data to determine the superiority of one method over the other. 

In patients with bulky disease or a significant tumor burden, neoadjuvant chemotherapy can be used to decrease tumor burden to increase the likelihood of optimal tumor debulking during surgery.35 Typically, three cycles of the standard combination taxane/platinum regimen is administered once every 3 weeks. After surgery, the patient will receive another three to six cycles depending on response to chemotherapy. 

Neoadjuvant or primary chemotherapy is the initial treatment of choice. Benefits include rendering inoperable tumors resectable and increasing the rate of BCT. 

The goal of neoadjuvant chemotherapy in locally advanced breast cancer is cure. Complete pathologic response, determined at the time of surgery, is the desired end point. 

For unresectable tumors, neoadjuvant (preoperative) 5-FU or capecitabine chemoradiation followed by surgery is recommended. All patients who receive preoperative chemotherapy should receive postoperative chemotherapy, with or without RT. 

Optimal management of locally advanced NSCLC (stages IIB, IIIA, and IIIB) is controversial. Cisplatin-based doublet combinations are recommended for adjuvant and neoadjuvant (preoperative) chemotherapy, with or without concurrent radiation therapy. 

Strauss GM, Herndon JE, Sherman DD, et al. Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage Ilia non-small cell carcinoma of the lung report of a Cancer and Leukemia Group B phase II study. J Clin Oncol 1992 10 1237-1244. 

The MACH-NC study included a subset analysis of six randomized trials of 861 patients evaluating neoadjuvant with or without adjuvant chemotherapy combined with radiotherapy vs concomitant/alternating chemotherapy. No significant benefit was associated with adjuvant or neoadjuvant chemotherapy. A trend in favor of concomitant or alternating chemoradiotherapy was found but was not determined to be statistically significant (p =... 

El Sayed and Nelson reviewed 42 trials between 1963 and 1993 including six trials prior to 1965 and one trial using razoxane, a nonstandard chemotherapy agent (73). A drawback to the El Sayed analysis is the inclusion of a single trial that had been accounted for twice because of its publication in two different journals. The addition of chemotherapy to locoregional treatment added an absolute benefit of 4.0% absolute benefits of concomitant chemotherapy were 8% (neoadjuvant and adjuvant chemotherapy were not assessed). 

Postoperative Radiation Therapy Postoperative Chemotherapy or Chemoradiation NeOADJUVANT THERAPY, In GENERAL Preoperative Radiation Therapy Preoperative Chemotherapy Preoperative Chemoradiation... 

Studies have found that the patients who respond to neoadjuvant chemotherapy have prolonged survival over nonresponders (median 20 vs 6.2 mo) (28). The pathologic complete response rates in studies of neoadjuvant chemotherapy alone have been a dismal 10%. More recent studies have involved the addition of neoadjuvant radiation to chemotherapy to improve on these results. 

In the neoadjuvant setting, radiation, as well as chemotherapy, can be delivered to more well-oxygenated tissue and thereby enhance the ability to kill tumor cells. 

Intensified Neoadjuvant Chemotherapy Followed by Intensified Chemoradiotherapy... 

A phase II Intergroup study (INT0122, ECOG PE289, RTOG 9012) increased the intensity of both chemotherapy and radiation. The neoadjuvant chemotherapy consisted of three courses of cisplatin and 5 -FU followed by concurrent chemoradiation consisting of two additional courses of cisplatin and 5-FU and radiation, 6480 cGy/36 fractions. 

Vanderbilt University Medical Center has recently completed accruing patients to a Phase II study of neoadjuvant chemoradiation, which consists of preoperative paclitaxel (175 mg/m2,3-h infusion) followed by cisplatin 75 mg/m2 d 1 and 21. Concurrent radiation was given to a total dose of 3000 cGy, in 200 cGy/fraction. Patients who are resectable go on to surgery 4 wk after completion of chemoradiation, whereas those who are unresectable (i.e., cervical esophageal cancer) continue to a total dose of 60 Gy without treatment interruptions. One month following surgery, patients receive two cycles (q 21-28 d) of postoperative chemotherapy, which consists of paclitaxel 175 mg/m2 over 3 h d 1,5-FU 350 mg/m2, d 1-3, and leucovorin 300 mg d 1-3. Preliminary analysis of this... 

Kok T, Lanschot J, Siersema P, et al. Neoadjuvant Chemotherapy in Operable Esophageal Squamous Cell Cancer Final Report of a Phase III Multicenter Randomized Controlled Trial. Proc Am Soc Clin Oncol 1997 16 277a. 

Minsky BD, Neuberg D, Kelsen DP, et al. Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12) Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys 1999 43(3) 517—523. 

---