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PubMed2004

Neoadjuvant therapy for pancreatic cancer: the Duke experience.

The advantages of neoadjuvant (preoperative) chemoradiation therapy for pancreatic cancer include the assurance that all resected patients receive multimodality therapy; the opportunity for patients with occult metastatic disease to manifest themselves; and the potential to improve resectability. Since 1994, Duke University Medical Center has treated over 180 patients with localized pancreatic cancer using neoadjuvant 5-fluorouracil (5FU)-based chemoradiation therapy (CRT). Approximately 20% of patients demonstrate distant disease progression during CRT and avoid the morbidity of laparotomy. Almost 20% of locally advanced tumors on initial-staging CT can be resected following CRT. Patients who have successfully undergone resection have experienced favorable survival with an estimated 5-year survival rate of 36%. This article reviews the authors' experience and the lessons learned from it.

Adult↗
PubMed2001

Adjuvant and neoadjuvant therapy for early stage non-small cell lung cancer.

Lung cancer is the number one cause of cancer-related death in both men and women in the United States. Non-small cell lung cancer accounts for approximately 85% of these cases. Despite complete resection, long-term survival for patients with operable disease remains poor. Studies exploring postoperative chemotherapy have not shown improved survival. Preoperative chemotherapy has shown promise in stage III disease and is currently under investigation for patients with early stage non-small cell lung cancer.

Antineoplastic Agents↗
PubMed1998

[Cancer of the esophagus: outcome of neoadjuvant therapy on surgical morbidity and mortality].

Prognosis of oesophageal cancer is poor. There have been phase II-III trials of postoperative chemotherapy with the aim of improving survival. Chemoradiotherapy seems more promising than both chemotherapy and radiotherapy alone. In contrast, better results obtained with chemoradiotherapy were associated with an increase in morbidity and mortality, and finally overall survival was uncommonly improved. It is necessary to implement new multidisciplinary randomised trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Neoadjuvant therapy before radical prostatectomy: where have we been? Where are we going?

Prostate cancer is curable only when treated at an early stage, when the tumor is still localized to the prostate gland. However, even in apparent cases of clinically localized disease, unsuspected extracapsular disease may significantly increase the risk of primary treatment failure. This risk is especially high if the patient has > or =1 of the following risk factors: a serum prostate-specific antigen level of >20 ng/ml, a Gleason score of >7, locally advanced disease (clinical stage T3/T4), and extensive disease on prostate biopsy. Various regimens of neoadjuvant hormonal therapy, chemotherapy, or both have produced mixed results and, in general, have not significantly influenced the rate of disease relapse (as defined by prostate-specific antigen level) in high-risk patients with localized prostate cancer. In addition, anti-angiogenic agents, gene therapy, molecular targeting agents, and other promising new therapies have been investigated in a neoadjuvant setting with limited results. Therefore, this patient population continues to pose a therapeutic dilemma for physicians.

Humans↗
PubMed1998

[Radiation therapy with neoadjuvant hormonal therapy for prostate cancer confined to pelvis].

Neoadjuvant endocrine treatment prior to radical prostatectomy for prostate cancer confined to pelvis has of some value to prevent progression although there are many controversies. In order to improve the prognosis of locally advanced prostate cancer (stage B2 and C), definitive radiotherapy with neoadjuvant endocrine therapy has been investigated. Endocrine therapy reduces the volume of prostate, thus reduces the amount of side effect via reducing the area of irradiated normal tissue. Effect of radiation and that of endocrine therapy to induce apoptosis might be synergistic. The result is favorable although the follow-up period is too short. Further studies are needed to make conclusion.

Gonadotropin-Releasing Hormone↗
PubMed2003

[Indications for neoadjuvant therapy in rectal carcinoma].

Pre- and postoperative adjuvant treatments for locally advanced, operable (R0 resection) rectum carcinoma have led to improved results. In principle, according to the interdisciplinary consensus of the German Cancer Society, the recommended treatment for rectum carcinoma (T3/4; N0; M0; any T stage; N+; M0) is still postoperative adjuvant radiochemotherapy. In the meantime, however, based on the good results obtained from various clinical trials preoperative adjuvant treatment is favored internationally. Not only does this treatment scheme show a comparably better compliance of the patients but it also seems to be better tolerated. One treatment option for resectable T3 tumors immediately followed by surgery is the sole hypofractionated preoperative 3-4 field external beam radiotherapy. An additional benefit can be expected from protracted preoperative radiochemotherapy (single dose 2 Gy, total dose >40 Gy, chemotherapy based on 5-FU) followed by operation several weeks later. For T4 tumors with expected R1 or R2 resection, preoperative treatment is urgently recommended. A further aim in compliance with the surgical approach (R0 resection!) and multimodal treatment may be for individual cases the preservation of continence.

Antineoplastic Agents↗
PubMed2005

Adjuvant and neoadjuvant therapy for early-stage non-small-cell lung cancer.

Early-stage non-small-cell lung cancer (NSCLC) carries with it an unfavorable prognosis even in patients who have undergone surgical intervention. Efforts to improve the outcome of patients with early-stage NSCLC have focused on adjuvant or neoadjuvant chemotherapy. The role of adjuvant therapy in NSCLC has been clarified by the recent publication of several large randomized trials. The International Adjuvant Lung Trial was the first prospective trial to report that adjuvant chemotherapy following complete surgical resection of NSCLC improved absolute overall survival by approximately 5% at 5 years. This result has subsequently been confirmed by several other trials. As a result, adjuvant chemotherapy following complete resection of stage IB-III NSCLC can now be considered the standard of care. Neoadjuvant chemotherapy, which has long been investigated for stage III NSCLC, was also recently explored in stage I/II NSCLC. Although neoadjuvant chemotherapy seems promising, more work is needed to comprehensively evaluate and optimize this approach. The current evidence for adjuvant and neoadjuvant therapy in early-stage NSCLC is reviewed in this article.

Antineoplastic Agents↗
PubMed2005

Response to neoadjuvant therapy for rectal cancer: influence on long-term results.

OBJECTIVE: Pre-operative treatment with chemoradiotherapy (CRT) seems to improve local control and overall survival in patients with rectal cancer. The aims of the study were to analyse the impact on overall, disease free and cancer related survival of tumour response to pre-operative CRT and to analyse the influence of the degree of response on long-terms results. PATIENTS AND METHODS: Patients with a locally advanced rectal cancer, treated by pre-operative CRT were studied. A radical resection of the rectal tumour with mesorectal excision was performed within 6-8 weeks. Judged on the final TNM classification patients were considered responders when the tumour showed histologically a complete response, microscopic residual disease or a partial response. Non-responders were those in whom the extent of disease remained stable or progressed. Results Radical excision was performed in 103 patients, and a palliative resection in five. Forty-three patients underwent abdominoperineal resection and 65 anterior resection of the rectum. Seventy-one (65.7%) patients showed a response to CRT, while 37 (34.3%) did not. The overall local and distant recurrence rates were 6.8% and 21.3%. Tumour recurrence (P < 0.008) and disease free survival (P < 0.007) were significantly different in responders and nonresponders. Of the 71 responders, 16 had a pathological complete response, 27 had persisting microscopic disease and 28 had macroscopic residual disease. No differences in cancer specific outcome were observed in these groups. CONCLUSION: Pathological response to pre-operative CRT is associated with improved tumour recurrence and disease-free survival rates. Any response to pre-operative CRT appears to improve outcomes as much as a complete response.

Adult↗
PubMed2005

[Neoadjuvant therapy for squamous cell carcinoma of the esophagus].

Neoadjuvant treatment for locally advanced squamous cell carcinoma of the esophagus is widely used, despite minimal evidence of its efficacy. With only a minor effect on survival, the benefits of neoadjuvant radiotherapy alone appear to be limited. The same is true for neoadjuvant chemotherapy alone. While no single randomized study has shown a statistically significant result favoring neoadjuvant chemoradiation vs no treatment, the results of three meta-analyses indicate a prognostic benefit. Unfortunately, earlier chemoradiation protocols were associated with considerable side effects and contributed to perioperative morbidity and mortality. In contrast, modern chemoradiation protocols were revealed to be feasible when carried out in experienced institutions. Therefore, neoadjuvant chemoradiation is indicated in locally advanced stages. Patients should be referred to specialized centers for initial treatment planning and resection, and they should be enrolled in clinical studies whenever possible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Trimodality treatment in Stage III nonsmall cell lung carcinoma: prrognostic impact of K-ras mutations after neoadjuvant therapy.

BACKGROUND: In a trimodality treatment approach for Stage III nonsmall cell lung carcinoma (NSCLC), the prognostic impact of the ras mutation status in resection specimens was evaluated. METHODS: Forty patients with Stage III NSCLC underwent tumor resection after neoadjuvant treatment with two cycles of chemotherapy (ifosfamide, carboplatin, and etoposide) and subsequent twice-daily radiotherapy (45 grays [Gy]; 2 x 1.5 Gy/day) with concurrent carboplatin and vindesine. Assessment of K-ras codon 12 mutation status was performed in the paraffin embedded resection specimens by a two-step polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: K-ras mutation status could be assessed in 28 cases. A K-ras codon 12 point mutation was found in 13 of 28 resection specimens (46%). The mutation was found independently of gender, age, tumor stage, and clinical response status and occurred more frequently in adenocarcinomas. Even after complete resection, the presence of a K-ras mutation was a significant predictor for a poor progression free survival (P = 0.005). CONCLUSIONS: These data suggest that further evaluation of the K-ras codon 12 mutation status in trials on neoadjuvant and adjuvant therapy is warranted. This may contribute to the identification of stratification variables for future treatment approaches.

Adenocarcinoma↗
PubMed2003

Adjuvant and neoadjuvant therapy for esophageal cancer: a critical reappraisal.

Despite important refinements of surgical technique and significant progress in perioperative care, esophageal cancer remains highly lethal. Therefore, hope for improvement in the prognosis of esophageal cancer lies largely in the use of additional therapy. Promising data from numerous Phase II trials and a single Phase III trial led to the widespread adoption of neoadjuvant chemoradiotherapy. However, subsequent randomized trials did not conclusively demonstrate a survival benefit with any of the current neoadjuvant protocols for patients with resectable esophageal cancer. Benefit, if any, exists only for complete pathologic responders. Neoadjuvant chemoradiation should not be used in patients with resectable esophageal cancer outside of the clinical trials. Future investigation must focus on the development of new biologic or chemotherapeutic agents, and the identification of biologic markers that might predict response to chemoradiation.

Adenocarcinoma↗