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Results for “Neoadjuvant therapy”

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PubMed2000

Neoadjuvant hormonal ablative therapy before radical prostatectomy: a review. Is it indicated?

PURPOSE: Neoadjuvant hormonal ablation therapy has been used to decrease the rate of positive surgical margins in patients treated with radical prostatectomy. We reviewed the available literature to determine whether this therapy is indicated and beneficial. MATERIALS AND METHODS: We performed a MEDLINE key word search and assessed randomized prospective articles. Data were analyzed for the rate of positive surgical margins, seminal vesicle invasion and lymph node metastasis as well as surgical characteristics, including operative time, blood loss, hospital stay, rate of complications and difficulty of surgical dissection. In addition, these data were evaluated for prostate specific antigen-free survival. RESULTS: Neoadjuvant hormonal therapy decreased the rate of positive margins in 6 of the 7 randomized prospective studies. In none of 4 randomized prospective series was there an improved rate of seminal vesicle invasion with neoadjuvant hormonal therapy. Of 4 studies 3 showed no improvement in the rate of lymph node metastasis after neoadjuvant hormonal therapy compared with that in controls. Similarly there was no improvement in prostate specific antigen-free survival and no significant difference in operative time, operative blood loss, transfusion or hospital stay in patients treated with neoadjuvant hormonal therapy and controls. In addition, in 2 of 3 studies there was no difference in the complication rate. CONCLUSIONS: Analysis of the available literature revealed no significant improvement in outcome to support the routine administration of neoadjuvant hormonal therapy before prostatectomy.

Androgen Antagonists↗

PubMed2003

Chemotherapeutic advances in pancreatic cancer.

Advances in chemotherapy for pancreatic cancer have been limited. In the past decade, the standard therapy for metastatic disease has switched from 5-fluorouracil (5-FU) to gemcitabine. However, several other cytotoxic agents have shown limited but promising efficacy in pancreatic cancer, and many of these appear to be well suited for combination chemotherapy. Although 5-FU and cisplatin have not demonstrated substantial survival benefits when combined with gemcitabine, results of several phase III trials with other agents are still pending. For locally advanced disease, most recent studies have incorporated gemcitabine into combined-modality therapy. Similarly, in surgically resectable disease, current trials are incorporating gemcitabine into adjuvant therapy. Other trials are using neoadjuvant therapy as a possible means to improve upon current surgical results. However, much hope comes from the development of newer "targeted" therapies for this disease. Although matrix metalloproteinase inhibitors and farnesyl transferase inhibitors did not appear to be effective in initial studies, other targeted therapies are beginning to enter clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Thymoma: a multivariate analysis of factors predicting survival.

BACKGROUND: Despite complete surgical excision, malignant thymomas often recur with resultant death. We reviewed our series to determine which factors independently predict survival after surgical resection. METHODS: A retrospective analysis of patients operated on for thymoma between 1949 and 1993 at Memorial Sloan-Kettering Cancer Center was performed. Clinical data were collected from chart review. Only patients with a pathology report confirming the diagnosis of thymoma were included in this analysis. Kaplan-Meier survival curves were generated and comparisons of survival analyzed by log rank test. Multivariate analysis was performed by the Cox proportional hazard model. RESULTS: One hundred eighteen patients with thymoma underwent operation. There were 86 complete resections (73%), 18 partial resections (15%), and 14 biopsies (12%). By Masaoka staging, 25 patients were stage I (21%), 41 stage II (35%), 43 stage III (36%), and 9 stage IVa (8%). Overall survival was 77% at 5 years and 55% at 10 years. Tumor recurred in 25 (29%) of 86 completely resected thymomas. Stage of disease (p = 0.03) was the only independent prognostic factor affecting recurrence. By multivariate analysis, stage (p = 0.003), tumor size (p = 0.0001), histology (p = 0.004), and extent of surgical resection (p = 0.0006) were independent predictors of long-term survival. CONCLUSIONS: Patients with stage I disease require no further therapy after complete surgical resection. Neoadjuvant therapy should be considered for patients with large tumors and invasive disease.

Combined Modality Therapy↗

PubMed1994

[The clinical effect of chemotherapy with 5-FU and low-dose CDDP in patients with advanced gastric cancer].

A trial of FP therapy, a novel systemic chemotherapy consisting of 5-FU and low-dose CDDP, was carried out in patients with advanced gastric cancer and the clinical effects were evaluated. Five hundred mg/body/day of 5-FU was continuously administered via the central venous catheter for 7 consecutive days and 10mg/day of CDDP was rapidly administered with 500ml saline on days 1-5. The regimen was repeated for at least 4 weeks. The FP therapy was carried out in 22 cases, including several patients who underwent FP as an adjuvant therapy; 1 CR, 2PR's 1MR and 2NC's were obtained among the 6 patients with clinically evaluable lesions, resulting in a response rate of 50%. In four cases, the FP therapy was given as a neoadjuvant therapy, and histopathological examination of the resected specimen revealed histological effects exceeding Grade 2 in all 4 cases. Bone marrow suppression was the most commonly observed side effect, but renal dysfunction and nausea were not found. FP therapy is considered an effective therapy against advanced gastric cancer, from the viewpoint of both the clinical and adverse effects, in comparison with conventional regimen consisting of 5-FU and a single and large dose of CDDP.

Adenocarcinoma↗

PubMed2000

[Preoperative radiochemotherapy of esophageal carcinoma. Light at the end of the tunnel?].

Studies on neoadjuvant therapy of esophageal cancer showed that not either preoperative chemotherapy or radiotherapy lead to a significant improvement of prognosis. However, two prospective studies showed a significant prognostic improvement after neoadjuvant combined radio/chemotherapy. Most treatment protocols include a radiation with 30-45 Gy and a simultaneous therapy with Cis-Platin/5-Fluorouracil. As an increase of perioperative morbidity and mortality has to be expected through this treatment, a careful selection of patients is necessary. Several studies have shown that mostly patients with good response benefit from this neoadjuvant therapy. The clinical response evaluation is difficult and response is best proved by classification of the histomorphologic regression of the tumor. For future research, predictive response analyses based on molecular biologic and immuno-histochemic techniques are of great importance and first differentiations by biomarkers have been detected.

Adenocarcinoma↗

PubMed2005

One hundred consecutive pneumonectomies after induction therapy for non-small cell lung cancer: an uncertain balance between risks and benefits.

OBJECTIVE: We sought to assess postoperative outcome after pneumonectomy after neoadjuvant therapy in patients with non-small cell lung cancer. METHODS: This retrospective study included 100 patients treated from January 1989 through December 2003 for a primary lung cancer in whom pneumonectomy had been performed after an induction treatment. Surgical intervention had not been considered initially for the following reasons: N2 disease (stage IIIA, n = 79), doubtful resectability (stage IIIB [T4, N0], n = 19), and M1 disease (stage IV [T2, N0, M1, solitary brain metastasis], n = 2). All patients received a 2-drug platinum-based regimen with a median of 2.5 cycles (range, 2-4 cycles), and 30 had associated radiotherapy (30-45 Gy). RESULTS: There were 55 right and 45 left resections. Overall 30-day and 90-day mortality rates were 12% and 21%, respectively. At multivariate analysis, one independent prognostic factor entered the model to predict 30-day mortality: postoperative cardiovascular event (relative risk, 45.7; 95% confidence interval, 3.7-226.7; P = .001). Four variables predicted 90-day mortality: age of more than 60 years (relative risk, 5.06; 95% confidence interval, 1.47-17.48; P = .01), male sex (relative risk, 8.25; 95% confidence interval, 1.01-67.34; P = .049), postoperative respiratory event (relative risk, 3.64; 95% confidence interval, 1.14-9.37; P = .007), and postoperative cardiovascular event (relative risk, 7.84; 95% confidence interval, 3.12-19.71; P < .001). Estimated overall survivals in 90-day survivors were 35% (range, 29%-41%) and 25% (range, 19.3%-30.7%) at 3 and 5 years, respectively. At multivariate analysis, one independent prognostic factor entered the model: pathologic stage III-IV residual disease (relative risk, 1.89; 95% confidence interval, 1.09-3.26; P = .022). CONCLUSIONS: Pneumonectomy after induction therapy is a high-risk procedure, the survival benefit of which appears uncertain.

Adult↗

PubMed2006

[A long term survival case of advanced intrahepatic cholangiocarcinoma treated with multidisciplinary treatment].

A 56-year-old man was admitted to our hospital for liver tumor of 7 cm in diameter, located mainly in the anterior segment. He underwent a hepatic resection of anterior and median segment of the liver in January 2002. Pathologically, the tumor was moderately differentiated intrahepatic cholangiocarcinoma (ICC) with vascular invasion. Hepatic arterial chemotherapy as a neoadjuvant therapy was performed. In December 2002, bone metastases in the 12th thoracic spine and iliac bone were found. Therefore, he received radiotherapy (total of 30 Gy) and a monthly bisphosphonate infusion. In May 2003, multiple intrahepatic recurrences were diagnosed. Transarterial chemoembolization for twice and an additional radio-frequency ablation were performed. Four months later, lung metastases were found, thus, he was administered TS-1. He has been alive with PS 0 for 4 and half years after the hepatic resection. No new intrahepatic recurrences were found and bone and lung metastases remained to be stable. Although only a hepatic resection is a useful therapy for ICC, such a multidisciplinary treatment may have an effect to improve the prognosis of patients with ICC.

Bile Duct Neoplasms↗

PubMed1999

[Lung cancer].

The five year survival rate of lung cancer patients is only 10% in Japan. The staging system of c-TNM is more important than p-TNM when deciding treatment modality for lung cancer. Compared to other solid cancers, neoadjuvant therapy in lung cancer treatment has a more important position. A clinical protocol study should be carried out with the idea of "intent to treat" and medical oncology will play a more important role in the treatment of lung cancer.

Chemotherapy, Adjuvant↗

PubMed2001

Neoadjuvant chemotherapy with docetaxel in non--small cell lung cancer.

Based on proven activity and survival benefit in advanced non--small cell lung cancer, docetaxel has been introduced into neoadjuvant therapy. In a large, phase III randomized trial in 274 stage IIIA and IIIB patients, treatment with an induction regimen of 100 mg/m(2) docetaxel for three cycles before definitive surgery or radiotherapy was associated with an encouraging trend towards longer median survival. Overall 1-year survival was 59% compared with 51% in the control group. Docetaxel in the neoadjuvant setting was well tolerated and did not compromise later radical local therapy. The incidence of grade (3/4) esophagitis, for example, was less than 1% in patients who had had induction docetaxel followed by curative radiotherapy. This also was true for pneumonitis. Neoadjuvant docetaxel in combination with cisplatin or carboplatin is being evaluated in phase II trials which have reported response rates of 66% to 82% and rates of complete resection ranging from 69% to 79%. Docetaxel also is being investigated in combination with both cisplatin and gemcitabine in phase I/II studies. Phase III trials will further define the promising role of docetaxel alone and in combination in neoadjuvant therapy. Semin Oncol 28 (suppl 9):33-36.

Antimetabolites, Antineoplastic↗

PubMed2001

Letrozole as primary medical therapy for locally advanced and large operable breast cancer.

AIMS: To investigate the efficacy of letrozole 2.5 mg and 10 mg used as primary neoadjuvant therapy for patients with locally advanced and large operable breast cancer. PATIENTS AND METHODS: Twenty-four postmenopausal patients with locally advanced or large operable breast cancer were treated in two consecutive series with letrozole 2.5 mg (n = 12) or letrozole 10 mg (n = 12). Response at three months was measured by change in tumor volume according to WHO criteria (partial response was defined as a reduction in tumor volume > or = 65%). Tumor volumes were assessed clinically, by ultrasound and mammography, and pathologically. RESULTS: All 24 patients were estrogen receptor-positive, were considered 'receptor-rich', and mean age was 77.6 years and 71.6 years in the letrozole 2.5 mg and 10 mg treatment groups, respectively. There were five complete clinical responses and seven partial clinical responses in the patients treated with 2.5 mg letrozole, and nine partial responses and three patients with stable disease in patients treated with 10 mg letrozole. Assessed by ultrasound and mammography, the 12 patients treated with 2.5 mg had one complete response, nine partial responses and two with no change. In the 12 patients treated with 10 mg letrozole, imaging gave eight partial responses and four with no change. One patient treated with the 2.5 mg dose had a complete clinical and pathological response. There was no significant difference between the two doses in effect on tumor volume, and no recordable side effects associated with either dose. CONCLUSION: Letrozole used in a neoadjuvant setting is highly effective, producing clinically beneficial reductions in tumor volume allowing all patients to have breast conserving surgery, and has an acceptable safety profile.

Aged↗

PubMed2002

Neoadjuvant and adjuvant therapies for resectable hepatocellular carcinoma (HCC) and palliation strategies.

Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver worldwide. The incidence of the tumor varies geographically. Thus, in the eastern area (China, Taiwan, and Japan) there are more than 20 cases per year per 100'000 population compared to less than 5 cases per 100'000 in most western countries [1]. The etiology of HCC is multifactorial. The two most important factors are the presence of cirrhosis and chronic hepatitis [2]. Early detection of HCC still remains a challenge. At the time of diagnosis, only 20-30% of all patients have tumors that are surgically resectable. Survival after curative resection is 30%-50% at five years. The poor outcome of the disease led to the development of different adjuvant and neoadjuvant therapies. There are numerous studies dealing with the treatment of HCC. Unfortunately, only few randomized controlled trials exist. In addition, there is no consensus on staging of HCC and no standardization of the outcome in the literature, which makes it difficult to compare the different procedures. This paper summarizes the current strategies in the treatment of HCC.

Carcinoma, Hepatocellular↗

PubMed2004

Comparison of proliferating cell nuclear antigen immunostaining in lymph node metastases and primary prostate adenocarcinoma after neoadjuvant androgen deprivation therapy.

OBJECTIVE: To evaluate the effect of neoadjuvant androgen deprivation therapy (NADT) on the cellular proliferative activity in primary prostate cancer and lymph node metastases using proliferating cell nuclear antigen (PCNA) immunostaining. MATERIAL AND METHODS: Metastatic pelvic lymph nodes and tumoral prostatic tissue were obtained from 21 patients after radical prostatectomy and pelvic lymphadenectomy. Sixteen patients received NADT for 3 months prior to surgery; five patients did not and were evaluated as a control group. Histopathologic analysis was performed using PCNA immunostaining. and histopathologic findings of primary tumors and lymph node metastases after NADT were reported. Clinical follow-up was performed for a mean of 43.7 months. RESULTS: Evaluation of PCNA immunostaining of lymph node metastases in the 16 treated patients revealed a mean positivity for metastatic tumor of 4.5% (SD 3.1%); the corresponding value for the five patients who were not treated with NADT was 19.6% (SD 0.94%) (p < 0.05). In four of the treated cases the proliferative activity in the lymph node metastases was greater than that in the other 12 (9.3% and 3.0%, respectively) and no histopathologic regressive changes were observed in these four cases. The residual tumoral proliferative activity in lymph nodes was greater than that in primary tumors (4.5% and 1.3%, respectively). CONCLUSIONS: This study shows that the nodal metastases were responsive to hormonal therapy, as assessed by PCNA staining, although a greater residual proliferative activity was observed after NADT in lymph node metastases in comparison with the primary prostatic tumor. This can be attributed to a metastatic phenotype less responsive to hormonal therapy compared to the primary tumor.

Adenocarcinoma↗

PubMed1999

Correlation between EGFR and c-erbB-2 oncoprotein status and response to neoadjuvant chemotherapy in cervical carcinoma.

Neoadjuvant chemotherapy prior to definitive radical surgery or radiotherapy may be effective in reducing tumor volume or clinical stage and may even enhance pelvic control and survival. However, there are significant limitations to the use of neoadjuvant therapy in the non-responder group. They include delayed total treatment course, the presence of drug resistant clones which result in accelerated tumor growth, and limited bone marrow reserve for subsequent definitive therapy. Thus, there is a need to identify parameters providing a more precise indication of the response to neoadjuvant chemotherapy in patients with invasive cervical cancer. From Jan. 1995 to Jan. 1996, neoadjuvant chemotherapy with 3 courses of cisplatin and vincristine was used in 32 patients with invasive cervical cancer (FIGO stage Ib to IIIb; tumor size greater than 2 cm). Prior to chemotherapy, quantitative tissue levels of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene protein were measured by using an enzyme-linked immunosorbent assay (ELISA). Tumor size was estimated before and after chemotherapy. Relations between oncoproteins and reductions of tumor size were evaluated. Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c-erbB-2 oncoprotein. As well, the tumor reduction index did not manifest any correlation with EGFR, it did had an inverse linear correlation with the c-erbB-2 oncoprotein levels (Rs = -0.71, P < 0.05). The results of this study suggest that c-erbB-2 oncoprotein is associated with a reduced response to neoadjuvant chemotherapy in primary treatment of invasive cervical cancer and may be useful in directing therapeutic approaches.

Adult↗

PubMed2004

Neoadjuvant treatment of oesophageal adenocarcinoma.

Oesophageal adenocarcinoma is an enigma. It has emerged, seemingly from nowhere, in the late 20th century to dominate the oesophageal oncological landscape. This review will examine whether the current outcome for adenocarcinoma is as good as it gets or whether additional treatment is necessary and if so whether neoadjuvant therapy is effective.

Adenocarcinoma↗

PubMed2002

Sentinel node biopsy after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: After neoadjuvant chemotherapy, while results of sentinel node biopsy (SNB) are encouraging, conditions that may affect sentinel node (SN) detection and false negative rates with respect to clinical and pathological tumor response after neoadjuvant therapy require investigation. METHODS: Thirty-four patients with clinical stage I, II and IIIA invasive breast cancer underwent neoadjuvant chemotherapy with doxorubicin/cyclophosphamide or doxorubicin/cyclophosphamide and docetaxel/segmental resection, SNB, and axillary node dissection (AND). RESULTS: SNs were found in 31 of 34 patients (91.2%). SNs were found in 20 of 21 patients (95.2%) with complete clinical tumor response, it was positive in 40% and no false negatives occurred. SNs were found in 11 of 13 patients (84.6%) with partial or no clinical tumor response; in four patients (33%) the SN was positive and no false negative nodes were found. Seven patients had complete pathological tumor response. SNs were found in six of these patients (85.7%). The SN was positive in 1 of 6 patients (16.7%) with no false negative. In 25 of 27 patients (92%) with partial or no pathological tumor response, the SN was identified. Eleven of these patients (44%) had positive nodes with no false negatives. CONCLUSIONS: SN identification rate and accuracy after neoadjuvant chemotherapy for breast carcinoma were extremely good however there is potential for inaccuracy after less than complete pathological tumor response. Further evaluation of SNB in larger clinical trial is warranted prior to accepting this approach as a standard care.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: is there a benefit in using functional imaging?

The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and (18)F-FDG-PET (n=23) before and 2-4 weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60+/-14%) was significantly higher than in nonresponders (37+/-31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.

Adenocarcinoma↗

PubMed2005

How accurate is magnetic resonance imaging in restaging rectal cancer in patients receiving preoperative combined chemoradiotherapy?

PURPOSE: Preoperative combined chemoradiotherapy is currently the main neoadjuvant therapy used to treat locally advanced middle and low rectal adenocarcinoma. A restaging work-up with magnetic resonance imaging was hoped to provide information about the effects related to combined chemoradiotherapy. The goal was to evaluate the correlation between pathologically verified tumor stages and clinical stages predicted by magnetic resonance imaging after combined chemoradiotherapy. METHODS: Between August 2000 and June 2003, 50 patients with biopsy-proven middle and lower rectal adenocarcinoma, with initial stage T3-T4 or N+, M0, were recruited in this series. Pelvic magnetic resonance imaging was used to stage the tumor before and after combined chemoradiotherapy. A protocol of the standard external radiation dose and oral combined uracil and 5-fluorouracil plus leucovorin was used. The results of magnetic resonance imaging restaging after combined chemoradiotherapy were correlated with the pathologic staging. RESULTS: The overall predictive accuracy in T stage was 52 percent, whereas overstaging and understaging occurred in 38 percent and 10 percent of patients, respectively. Most of the inaccurate T staging was a result of the overstaging of superficial tumors (T0-T2). In N stage, accurate staging was noted in 68 percent of all patients, whereas 24 percent were overstaged and 8 percent were understaged. CONCLUSION: In restaging irradiated tumors, magnetic resonance imaging had the accuracy of 52 percent in T stage and 68 percent in N stage. Poor agreement between post-combined chemoradiotherapy magnetic resonance imaging and pathologic staging was observed in both T (k = 0.017) and N (k = 0.031) stages. Most of the inaccuracy in both T and N stages was caused by overstaging. The problem with magnetic resonance imaging was believed to be that it could not completely differentiate fibrosis from viable residual tumors.

Adenocarcinoma↗

PubMed2002

[Neoadjuvant therapeutic principles guided by response prediction and evaluation].

Only patients with a clinical and pathohistological response to neoadjuvant therapy have a significantly improved survival. Therefore the identification of predictors for response and procedures for the early identification of nonresponders appear to be mandatory. Preliminary data of biochemical investigations of target enzymes for several cytostatics (e.g. TS, ERCC1) appear to be promising. Early changes of the tumor metabolism in the FDG-PET enable the identification of nonresponders with a negative predictive value of 88-95%. In near future these findings should lead to consequences in the design and realization of clinical studies.

Adenocarcinoma↗