Year: 2007
Type: article
Abstract: We thank Dr. Gemici for his interest in our article.1 We agree that induction chemotherapy alone achieves pathologic response less often than preoperative chemoradiation. On the other hand, a meaningful response in patients with significant tumor burden may be difficult to achieve with chemoradiation alone secondary to the attenuated doses of chemotherapy necessarily administered with radiation. Our hypothesis has been that the addition of induction chemotherapy prior to (but not excluding) neoadjuvant chemoradiation would reduce the primary tumor volume and delay the appearance of metastases. Our intentions, contrary to the interpretation by Dr. Gemici, have never been to compare induction chemotherapy alone with preoperative chemoradiation. Our data, albeit retrospective, suggests that the addition of induction chemotherapy improves overall survival and disease-free survival, and this benefit is most apparent in patients with advanced disease. A previous analysis performed on patients who received neoadjuvant therapy showed a trend toward achieving complete pathologic response (pathCR) more often in patients who had received induction chemotherapy compared with the group that did not.2 However, even though pathCR is associated with the best results, a partial response may also be associated with prolonged survival. Another recent publication by our group established that a pathologic response to neoadjuvant chemoradiotherapy was an independent predictor of survival and that patients with 50% or less tumor viability in the resected specimen showed significantly better survival than nonresponders.3 The article under discussion1 shows that the number of patients who had a clinically meaningful response (complete or partial) was significantly better with the addition of induction therapy (64% versus 51%, P = .035), and this was associated with improved overall survival. We do not expect induction chemotherapy to reduce the rate of distant metastases simply because we do not believe that the currently available combinations of drugs are curative. Effective combination chemotherapy is expected to delay the appearance of metastases and only rarely eliminate them. Induction chemotherapy is not harmful as is being proposed; on the contrary, it has recently been shown to increase survival of gastroesophageal cancer patients4 and has not had an adverse impact on surgical outcomes or resectability.5 Finally, the suggestion that induction chemotherapy may result in repopulation of tumor with resistant clone is interesting, but conjectural, and this hypothesis would require in-depth serial molecular studies to understand the repopulation dynamics in the depleted tumor. At present, there is no evidence that induction chemotherapy administered before preoperative chemoradiation is harmful; however, its potential benefits for gastroesophageal cancer are currently being studied prospectively in Europe and the United States. Wayne Hofstetter MD*, Jaffer Ajani MD*, Stephen G. Swisher MD*, * Departments of Thoracic and Cardiovascular Surgery and Gastrointestinal Medical Oncology The University of Texas M. D. Anderson Cancer Center, Houston Texas.
Source: Cancer
DOI: 10.1002/cncr.22515
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2609190505