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Neoadjuvant therapy.

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Antineoplastic Agents↗
PubMed2006

[HPV-infection in esophageal cancer as possible predictive factor after neoadjuvant therapy].

BACKGROUND: Human papilloma virus (HPV) infection in oesophageal cancer cases was found 0-67% depending on different methods and geographical variances. Complete pathological response was in 30% of cases after neoadjuvant chemo-radiation (CRX). The aim of this study was to discover a possible relation between HPV-infection and response. MATERIAL AND METHODS: DNA was extracted from 26 oesophageal cancer patients undergoing CRX and surgery. PCR and Southern Blot hybridisation was used to detect HPV-infection (HPV-16 and -18). Clinicopathological parameters and disease-free survival and overall survival was also analysed. RESULTS: Complete response (26.9%) and partial response (38.5%) after CRX was correlated significantly with better prognosis. 6 patient had HPV-infection (3 from CR- and 3 from PR-group). CONCLUSIONS: There was a correlation between HPV-infection and response, but further analysis is necessary. Both responder-groups had significantly better prognosis than non-responders.

Antineoplastic Agents↗
PubMed2001

Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal.

BACKGROUND: Surgical resection is the most effective treatment for colorectal liver metastases but only a minority of patients are candidates for a potentially curative resection. Our experience with neoadjuvant chemotherapy followed by resection and five years survival analysis of the patients treated is presented. METHODS: Between February of 1988 and September of 1996, 701 patients with unresectable colorectal liver metastases were treated with neoadjuvant chemotherapy. Four categories of nonresectable disease were defined: large size, ill location, multinodularity, and extrahepatic disease. Liver resection was performed in those patients whose disease became resectable. After resection, the patients were followed up every 3 months. A 5-year survival analysis by the different categories described was performed. RESULTS: Ninety-five patients (13.5%) were found to be resectable on reevaluation and underwent a potentially curative resection. There was no perioperative mortality, and the complication rate was 23%. As of December of 1999, 87 patients have completed 5 years of follow-up. The overall 5-year survival is 35% from the time of resection and 39% from the onset of chemotherapy. Respective 5-year survival rates are 60% for large tumors, 49% for ill-located lesions, 34% for multinodular disease, and 18% for liver metastases with extrahepatic disease. In this latter category, however, a 35% 5-year survival was found when all the patients with extrahepatic disease were analyzed rather than only those for whom extrahepatic disease was the main cause of nonresectability. CONCLUSIONS: Neoadjuvant chemotherapy enables liver resection in some patients with initially unresectable colorectal metastases. Long-term survival is similar to that reported for a priori surgical candidates.

Adult↗
PubMed2004

[Neoadjuvant therapy of breast cancer].

Whereas in the past primary systemic therapy (PST) was rather used for other tumor entities or was limited to the use in inoperable breast cancer, treatment of operable stages is being increasingly investigated. After the proof of equivalency between PST and adjuvant chemotherapy, numerous trials have been conducted. PST enables testing of in vivo chemosensitivity; thus, treatment can be monitored by tumor response. Insufficient responders can be switched to non-cross-resistant concepts to avoid administration of ineffective drugs and try to achieve improvement of survival for these patients. The reduction of tumor size not only increases the rate of breast-conserving therapy, but has predictive value for the further course of the disease. Especially pathohistological complete remission is a good surrogate marker for improved survival and the goal of modern protocols in the preoperative setting. Actively recruiting trials (e.g. trials of the AGO PREPARE and TECHNO) integrate modern concepts of treatment like dose-dense, dose-intensified, sequential therapy and tumor targeting with trastuzumab in PST. Eligible patients should be recruited in ongoing trials to further elucidate the role of PST in primary breast cancer. Evaluation of predictive factors and correlation of therapy response to the genetic profile of the tumor with modern technologies will allow improved selection of patients with increasingly tailored therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation.

Chemoradiation is now used more commonly for gastric cancer following publication of the US Intergroup trial results that demonstrate an advantage to adjuvant postoperative chemoradiotherapy. However, there remain concerns regarding the toxicity of this treatment, the optimal chemotherapy regimen and the optimal method of radiotherapy delivery. In this prospective study, we evaluated the toxicity and feasibility of an alternative chemoradiation regimen to that used in the Intergroup trial. A total of 26 patients with adenocarcinoma of the stomach were treated with 3D-conformal radiation therapy to a dose of 45 Gy in 25 fractions with concurrent continuous infusional 5-fluorouracil (5-FU). The majority of patients received epirubicin, cisplatin and 5-FU (ECF) as the systemic component given before and after concurrent chemoradiation. The overall rates of observed grade 3 and 4 toxicities were 38 and 15%, respectively. GIT grade 3 toxicity was observed in 19% of patients, while haematologic grade 3 and 4 toxicities were observed in 23%. Our results suggest that this adjuvant regimen can be delivered safely and with acceptable toxicity. This regimen forms the basis of several new studies being developed for postoperative adjuvant therapy of gastric cancer.

Adenocarcinoma↗
PubMed2005

Phase I trial of capecitabine and weekly irinotecan in combination with radiotherapy for neoadjuvant therapy of rectal cancer.

PURPOSE: To establish the feasibility and efficacy of capecitabine in combination with weekly irinotecan (CAPIRI) with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer. PATIENTS AND METHODS: Nineteen patients with rectal cancer clinical stage T3-4, Nx received weekly irinotecan 50 mg/m(2) (days 1, 8, 15, 22, 29) and two doses of capecitabine (days 1 through 38; dose level [DL] I, 500 mg/m(2) bid; DL II, 625 mg/m(2) bid) according to phase I methodology. Three-dimensional conformal RT was given to a dose of 50.4 Gy (45 Gy + 5.4 Gy). RESULTS: On DL I, no dose-limiting toxicities occurred, whereas diarrhea grade 3 affected three of seven patients on DL II. Twelve patients were treated on DL I and received a median relative dose-intensity of 100% for both drugs. Grade 3 or 4 adverse events were observed in only one of these patients (asthenia grade 3). All patients underwent surgery and R0 resection was achieved in all patients. Pathologic complete remission was observed in four patients and another five patients had only microfoci of residual tumor. CONCLUSION: Preoperative chemoradiotherapy with CAPIRI is feasible and well tolerated. The preliminary efficacy is good, and the tolerability is at least comparable with data for fluorouracil plus irinotecan chemoradiotherapy. Larger phase II trials of the CAPIRI-RT schedule clearly are warranted.

Adult↗
PubMed2000

Neoadjuvant therapy and surgical resection for locally advanced non-small cell lung cancer.

During the past 15 years, treatment of stage IIIA (N2) non-small cell lung cancer has evolved considerably because of improvements in patients selection, staging, and combined modality therapy. Results of several clinical trials suggest that induction chemotherapy or chemoradiation and surgical resection is superior to surgery alone. However, the optimal induction regimen has not been defined. An intergroup trial is also underway to determine whether chemoradiation and surgical resection leads to better survival than chemotherapy and radiation alone. Future studies will assess ways to combine radiation and novel chemotherapeutic agents, and will identify molecular abnormalities that predict response to induction therapy.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Randomized trial of neoadjuvant therapy for lung cancer: interim analysis.

The role of neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer remains undefined. Since 1987, 27 patients with non-small cell lung cancer, all with histologically confirmed metastases to the ipsilateral mediastinal lymph nodes, have been enrolled in an ongoing prospective, randomized trial at our institution. Thirteen patients have been randomized to preoperative etoposide-platinum (EP) chemotherapy-surgery-postoperative EP, and 14 other patients have been randomized to surgery-postoperative mediastinal irradiation (SRT). Both groups are similar in sex, age, weight loss, tumor location, preoperative pulmonary function, physiologic grade, and tumor histology. Eight of the 13 EP patients have responded as evidenced by a 50% or greater radiographic tumor shrinkage after two cycles. Complete tumor and nodal resection rates were similar: 11/13 EP patients versus 12/14 SRT patients. There was no operative mortality for the 27 patients. Median potential follow-up is 29.9 months for the EP group and 34.9 months for the SRT group. Preliminary results suggest a trend toward increased survival time for the EP group (median, 28.7 months) versus the SRT group (median, 15.6 months) (p2 = 0.095). Eleven of 12 resected SRT patients have had recurrence versus 8 of 11 resected EP patients. Time to recurrence reveals no significant differences between the two groups but a trend toward increased disease-free interval in the EP group (12.7 months versus 5.8 months, EP versus SRT). This interim analysis demonstrates the feasibility of such a trial; however, despite the trends, definitive conclusions await further accrual and study maturation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects.

OBJECTIVE: To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara) in patients with endometrial cancer. MATERIALS AND METHODS: Ten previously untreated, post-menopausal patients (mean age 59 years) with endometrial cancer, predominantly stage I disease, received letrozole 2.5mg per day for 14 days before surgery. Clinical, sonographic, morphologic, cytologic, and hormonal-metabolic parameters (blood estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and cholesterol by radioimmunoassay, enzyme immune assay, or enzyme-colorimetric methods; tumor progesterone receptors by ligand-binding assay; and aromatase activity by 3H-water release assay) were evaluated before and after treatment. RESULTS: Treatment was well-tolerated in all patients. In two patients, pain relief in the lower part of the belly and/or decrease in intensity of uterine discharge was reported. In the three cases, substantial decreases in endometrial M-echo (ultrasound) signal were noted; the mean value of this parameter after treatment was 31.1% lower than before treatment. Blood estradiol concentration decreased by an average of 37.8% after letrozole therapy, and tumor progesterone receptor levels and aromatase activity decreased by 34.4 and 17.5%, respectively. Treatment with letrozole did not influence surgery. CONCLUSIONS: These data show that short-term treatment with letrozole in the neoadjuvant setting resulted in some positive clinical changes. Longer-term and larger-scale trials of neoadjuvant letrozole in endometrial cancer are warranted.

Aged↗