Nuclear distribution of human DNA topoisomerase IIbeta: a nuclear targeting signal resides in the 116-residue C-terminal tail

Surgery is considered to be a standard therapy for stage III or the earlier stage of esophageal cancer. However, the standard therapy is changing because of the recent advances in the non-surgical approach, especially chemoradiotherapy. Various obstacles remain to estimate the outcomes of combined modality therapy, while the consensus of the treatment for such stage excluding T4 diseases are as follows: 1) Concurrent chemoradiotherapy has a superior outcome to radiation alone in patients with squamous cell carcinoma. 2) Recent chemoradiotherapy without surgery achieves results comparable to surgery alone. 3) Preoperative chemoradiotherapy can achieve better results than surgery alone in patients with adenocarcinoma. 4) Preoperative chemotherapy is still experimental. Our preliminary results of chemoradiotherapy for esophageal cancer also showed comparable data to extended surgery in terms of survival. Some significant points to be elucidated regarding combined modalities in stage III or earlier are: 1) the comparison of definitive chemoradiotherapy with Japanese extended surgery, and 2) evaluation of efficacy of surgery after chemoradiotherapy. However, these studies require randomized trials comparing surgery with non-surgical treatment, which appears to present significant obstacles. Critical estimation for each study should be recommended based on accurate clinical staging, biological behavior, and intention-to-treat.     

Diet supplemented with yoghurt or milk fermented by Lactobacillus casei DN-114 001 stimulates growth and brush-border enzyme activities in mouse small intestine

Adjuvant and neoadjuvant therapeutic principles have in recent years received increasing attention in the management of patients with carcinoma of the upper gastrointestinal tract. A series of randomized prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in gastric or esophageal cancer. The available data on the role of neoadjuvant preoperative therapy in these patients as yet permit no conclusion. While neoadjuvant therapy may reduce the tumor mass in a substantial portion of patients, a series of randomized controlled trials has shown that, compared to primary resection, a multimodal approach does not result in a survival benefit in patients with loco-regional, i.e. potentially resectable, tumors. In contrast, in patients with locally advanced tumors, i.e. tumors for which complete removal with primary surgery appears unlikely, neoadjuvant therapy increases the chance for complete tumor resection on subsequent surgery. However, only patients with objective histopathologic response to preoperative therapy appear to benefit from this approach. Compared to preoperative chemotherapy alone, combined radio-chemotherapy increases the rate of response, particularly in squamous cell esophageal cancer, but may also increase postoperative morbidity and mortality. Neoadjuvant therapy should therefore currently only be performed in experienced centers within the context of prospective clinical trials. The identification of factors that would allow prediction of response to neoadjuvant or adjuvant therapy is the focus of ongoing studies.     

Preoperative neoadjuvant chemotherapy with a combination of 5-fluorouracil, adriamycin and cisplatin (FAP) for advanced esophageal cancer invading trachea or main bronchus

Conventional irradiation and systemic chemotherapy is scarcely effective for advanced esophageal cancer invading trachea or main bronchus. Therefore, to reduce the area of invasion and suppress distant metastasis, we have preoperatively treated 4 patients suffering from advanced esophageal cancer invading the trachea or main bronchus by neoadjuvant chemotherapy (FAP) as follows: 2 times every 4 weeks, CDDP 100 mg and ADR 50 mg on day 1 and continuous infusion of 5-FU 1,000 mg/day for 7 days. The response rate (PR) was 75% (3/4). In 2 of 4 patients (50%), no cancer cells except broad fibrosis were detected histologically in the region of the trachea or main bronchus suspected to be invaded. There was no severe complication. This FAP regimen is suspected to be useful chemotherapy for advanced esophageal cancer.     

Male proportion in offspring of parents exposed to strong static and extremely low-frequency electromagnetic fields in Norway

Synchronized chemoradiation, where 5-FU and CDDP were synchronously administered in the same schedule with radiation therapy, was applied for advanced esophageal cancer in neoadjuvant fashion. Ten patients with advanced esophageal cancer were enrolled for this regimen consisting of 5-FU; 500 mg/day x 5/w x 4, CDDP; 10 mg/day x 5/w x 4 and radiation; 2 Gy x 5/w x 4. Tumor regression was achieved in all cases. In terms of toxicity, bone marrow suppression of more than grade 3 was observed in 60% of the cases, though it was safely controlled. Radical operation was performed on 8 cases. Histological responses in the resected specimen were as following: grade 3, 3 cases; grade 2b, 4 cases; grade 2a, 1 case; and 6 node-negative cases were found. As a postoperative complication, minor leakage occurred in 62.5%, while no major complications such as pneumonia were encountered. This neoadjuvant synchronized chemoradiation improved curability of the salvage operation and permitted reduction surgery for high-risk patients.     

Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma

PURPOSE: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. MATERIALS AND METHODS: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. RESULTS: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). CONCLUSION: Our results demonstrated that almost all early disease (Stage 0-I) and about half of advanced disease (Stage II-III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.     

Squamous cell carcinoma of the thoracic esophagus following radiation therapy for breast cancer

Between 1981 and 1995, 4 patients (3 females, 1 male; aged 48-80) were diagnosed with squamous cell carcinoma of the esophagus, following mediastinal irradiation for breast cancer. The interval between irradiation and the presentation of esophageal cancer was 10.75 years on average (7-19). The treatment consisted of: radiotherapy only; a partial esophagectomy with proximal gastrectomy without post-operative radiotherapy; laser photocoagulation for a superficial tumor; and, palliative treatment including gastrostomy, tracheal photocoagulation and chemotherapy for 1 patient suffering from advanced stage cancer with tracheal invasion, respectively. Radiotherapy of the esophageal cancer (exclusive or adjuvant) should take into account previous esophageal radiation therapy. The indications of curative excision surgery are the same as for other types of esophageal cancer, but the anastomoses should be performed in a non-irradiated area. Excision by esophageal stripping without thoracotomy is contraindicated because of the presence of peri-esophageal sclerosis. Preventive measures in radiation therapy for breast cancer are suggested.     

Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome

PURPOSE: To evaluate the 10-year outcome of patients with invasive (T2-3N0M0, staged according to the tumor, node, metastasis system) bladder cancer who responded completely to a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by bladder-sparing surgery. PATIENTS AND METHODS: Of 111 surgical candidates who received neoadjuvant MVAC, 60 (54%) achieved a complete clinical response (T0) on transurethral resection (TUR) of the primary tumor site. Of these, 28 requested follow-up with TUR alone, 15 had a partial cystectomy, and 17 elected a radical cystectomy. The patients were followed up for a median of 10 years (range, 8 to 13 years). RESULTS: Of 43 patients who had bladder-sparing surgery, 32 (74%) are alive, which includes 25 (58%) with an intact functioning bladder. Twenty-four patients (56%) developed bladder tumor recurrences from 5 to 96 months, which were invasive in 13 (30%) and superficial in 11 (26%). Thirteen patients required a salvage cystectomy, of whom 6 died, which includes 4 (9%) from a new invasive neoplasm. Of the 17 patients who had radical cystectomy, 11 (65%) are alive. CONCLUSION: The majority of patients with invasive bladder tumors who achieve T0 status after neoadjuvant MVAC chemotherapy preserve their bladders for up to 10 years with bladder-sparing surgery. The bladder remains at risk for new invasive tumors. Cystectomy salvages the majority, but not all, of relapsing patients.     

Neoadjuvant chemoradiotherapy for esophageal cancer: is it worthwhile?

BACKGROUND: With promising results from several institutions, many centers began treating patients with esophageal cancer with neoadjuvant chemoradiotherapy (NC) followed by esophagectomy. This approach is demanding for the patient and has not been proved to be better than esophagectomy alone. OBJECTIVE: To assess survival time and measures of quality of life associated with NC. DESIGN: A retrospective review during 1990 to 1996. SETTING: The 3 tertiary academic hospitals affiliated with the University of Massachusetts Medical School, Worcester. PARTICIPANTS: All patients (N=51) with cancer of the middle or lower esophagus who were treated with NC followed by esophagectomy during this period. MAIN OUTCOME MEASURES: Median and 1-, 2-, and 3-year survival times; median preoperative treatment time (first office visit for surgical consultation before beginning NC to the date of surgery), median hospital stay, and postoperative swallowing function. RESULTS: The median survival time of all patients was 16.3 months; 1-, 2-, and 3-year overall survival rates were 67%, 46%, and 39%, respectively. The median hospital stay was 12 days. The median postoperative treatment time was 3.3 months, which was 20% of the median survival time. Of the 51 patients, 19 were alive with a median follow-up time of 2.5 years. Twenty-nine percent of the patients had a complete pathological response with median and 1-, 2-, and 3-year survival rates of 17.5 months, 73%, 57%, and 57%, respectively. Palliation of dysphagia was excellent, with 44 (93%) of 47 operative survivors taking either a soft diet (18 [38%]) or a regular (26 [55%]) diet by the first postoperative visit. CONCLUSIONS: Median survival time with NC followed by esophagectomy for resectable cancer of the esophagus does not appear to be significantly better than that reported for esophagectomy alone. Further, treatment time with NC consumed 20% of survival time. Examining only these outcome variables suggests that NC is not worth-while. However, examining a longer-term outcome survival variable, such as 3-year survival time, suggests that NC followed by esophagectomy may result in greater long-term survival than that reported for esophagectomy alone. We conclude that further randomized, controlled studies are necessary before NC followed by esophagectomy is considered superior to esophagectomy alone for the treatment of resectable esophageal cancer.     

Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study

OBJECTIVE: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma. We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates. METHODS: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m2) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor). The mean age was 62 years, and 32 patients (80%) had adenocarcinoma. Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater). RESULTS: The average hospitalization for induction treatment was 17 days. Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication. The maximum tolerated dose of paclitaxel was 100 mg/m2. Two patients died during induction treatment. Thirty-six patients (90%) underwent resection. The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response. Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076). The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months. CONCLUSIONS: Paclitaxel at a dose of 100 mg/m2 appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival.     

A sensitive assay for studying dopaminergic activity in cultures of rat pituitary cells

Nine male patients with separate primary cancers of the esophagus and head and neck (pharynx, larynx) presented with a mean age of 56 years (41-69). They included 7 pharyngeal cancer patients and 2 laryngeal ones. Esophageal cancer was discovered synchronously in 6 patients and metachronously in 3 (1, 4, and 11 years later, respectively). The head and neck cancer was stage-I in one patient, stage-II in 4 and stage-IV in 4. The esophageal cancer was cervical in 2, thoracic in 6 and abdominal in 1. It was early cancer (stage-0) in 6 patients and advanced (stage-IV) in 3. The esophageal cancer was more advanced in the metachronous group, while it was early in the synchronous group. Since the head and neck cancer was advanced, all patients underwent a total laryngectomy for their head and neck cancers. As for esophageal surgery, a transhiatal esophagectomy was, in principle, performed for early cancers while a total thoracic esophagectomy was done for advanced cancers. For the reconstruction of the esophagus, a gastric tube was used. Four patients are still alive with a mean survival time of 25 months, whereas five died of cancer recurrence of either type a mean of 19 months after surgery. As compared with the survival rates of the patients with esophageal cancer alone, the 5-year survival rate was 18.2% for patients with double cancers in this series and 27.9% for those with esophageal cancer alone.     

Malignant tracheoesophageal fistula in patients with esophageal cancer

BACKGROUND: Patients with esophageal cancer and a malignant tracheoesophageal fistula (TEF) have an extremely poor prognosis. Additionally, these patients often are denied treatment with radiation therapy because there is concern that these treatments may increase the size and associated problems of the TEF. METHODS: To determine the appropriate treatment (use of radiation therapy) for patients with esophageal cancer and malignant TEF, a review was performed of all such cases seen at the Mayo Clinic between 1971 and 1991. RESULTS: Between 1971 and 1991, 41 patients with malignant TEF arising as a result of esophageal cancer were seen at the Mayo Clinic in Rochester. Twenty-eight of these cancers were locally recurrent, and this group of patients had a uniformly poor outcome (median survival time, 1.4 months). Thirteen patients had a malignant TEF and had not received previous treatment for their esophageal cancer. The median survival length was 4 months for this group of patients. Of the 41 patients in this study, 10 received radiation therapy for their malignant TEF (30-66 Gy). The median survival length of this group of patients was 4.8 months. Six of these 10 patients died of metastatic disease (median survival length, 9 months), and there was no evidence of progression of the local tumor. Four of these 10 patients died of local progression of the malignancy (median survival length, 3 months). CONCLUSIONS: Radiation therapy did not increase the severity of the TEF. The authors conclude that radiation therapy can be administered safely in patients with TEF resulting from esophageal cancer. In some patients, radiation treatment may contribute to stabilization of the local tumor process (60% of patients treated with radiation therapy died of metastatic disease without local progression of tumor); however, all patients in this study eventually died of esophageal cancer.     

Cancer of the oesophagus

Oesophageal cancer is the fourth most common tumour in developing countries, comprising mainly squamous cell tumours, although the incidence of adenocarcinoma has increased enormously over the last decades. Surgical resection has long been acknowledged as the mainstay of treatment, and developments in surgical technique are reviewed. The roles of radiotherapy and chemotherapy in the management of oesophageal cancer remain unclear, especially as the majority of studies to date have been uncontrolled trials. We present an analysis of 601 patients who underwent resection for carcinoma of the oesophagus between 1970 and 1994 in the Department of Clinical Surgery, St James's Hospital, Dublin. The analysis shows clearly that, while peri-operative mortality continues to improve, conventional surgery offers little prospect of cure in the majority of cases. We have therefore embarked upon a prospective controlled trial of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone in patients with adenocarcinoma or squamous cell tumours of the oesophagus. Preliminary results indicate that multi-modality treatment may have a valuable role to play in the treatment of carcinoma of the oesophagus.     

The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Impact of androgen deprivation prior to radical prostatectomy for T1, T2 prostate cancer on the likelihood of curative surgery

BACKGROUND: Extracapsular extension is commonly seen in patients undergoing radical prostatectomy for localized prostate cancer due to understaging of disease. One possible approach to reduce the likelihood of extracapsular disease is androgen deprivation prior to radical prostatectomy, neoadjuvant therapy. However, adequate application is not clear. We analyzed the outcome of neoadjuvant therapy and radical prostatectomy in an attempt to expand our understanding on indications of neoadjuvant therapy. METHODS: Forty-six selected patients with clinical T1 or T2 prostate cancer were retrospectively reviewed. Twenty-two patients underwent neoadjuvant therapy (group N) that mainly consists of LH-RH agonist. The duration of neoadjuvant therapy, varied from 1 to 12 months with the mean being 4 months. Twenty-four underwent radical prostatectomy alone (group S). RESULTS: In the group N and group S, 59% and 33% had either organ confined disease (OCD) or specimen confined disease (SCD) respectively. When the patients had OCD or SCD, they were defined as surgically cured patients. In the patients with clinical stage T1b, T1c, and T2 disease, likelihood of surgical cure were 100%, 50%, 46.7% in group N, 100%, 20%, 11%, in group S respectively. In the patients with initial serum PSA less than 10 ng/ml and more than 10.1 ng/ml, likelihood of surgical cure were 83.3% and 50% in group N, 63.6% and 15.4% in group S, respectively. Likelihood of surgical cure was higher in the patients with well differentiated carcinoma both in group N and group S. All the patients with serum PSA less than 0.1 ng/ml after neoadjuvant therapy had OCD. CONCLUSION: Neoadjuvent therapy could be beneficial either in the patients with moderately or in the poorly differentiated adenocarcinoma of prostate especially in the group with initial serum PSA more than 10.1 ng/ml. However, in patients both with well differentiated adenocarcinoma and the initial serum PSA less than 10 ng/ml, no evidence of beneficial effect on the likelihood of OCD or SCD was observed. PSA after neoadjuvant therapy could be useful predictor for the pathological outcome.     

Biology of esophageal cancer and the role of combined modality therapy

1. The biology of esophageal cancer involves multifactorial environmental and genetic events. 2. The understanding of the clinical significance of molecular markers is rapidly evolving. 3. Combined-modality approaches should still include surgery in good performance status (ECOG scale < or = 2) patients. 4. Neoadjuvant chemoradiation is probably better than surgical resection alone for patients with potentially curable disease, but only validation of this approach by CALGB-9781 can justify this as a new "proven" standard-of-care in the United States. 5. A pathologic complete response to neoadjuvant therapy is the strongest predictor of long-term survival. 6. 5-FU, by either short course or protracted continuous infusion, comprises the backbone of combination chemotherapy in combined-modality design. 7. Radiation therapy should be given at standard 1.8 to 2 Gy/fraction without a scheduled break. 8. Only by enrolling sufficient numbers of patients in prospective clinical trials will clinicians be able to further define the optimal sequencing and actual necessity of each individual component of combined-modality therapy.     

Accelerated fractionation in esophageal cancers: a multivariate analysis on 88 patients

PURPOSE: Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival. METHODS AND MATERIALS: Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days. RESULTS: The 3-year actuarial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%, and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grade 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control. CONCLUSION: These findings suggest that accelerated fractionation given in an overall treatment time of <35 days might be beneficial for early-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with moderate acute and late toxicity.     

Application and limitation of neoadjuvant hormonal therapy for prostate cancer

Of 156 patients, 111 (clinical stage T1a-b; 21, T1c; 17, T2a-b; 36, T2c; 27, T3; 10) immediately underwent radical prostatectomy (surgery group), and 45 (clinical stage T1a-b; 8, T1c; 4, T2a-b; 10, T2c; 9, T3; 14) received neoadjuvant hormonal therapy (NHT group). NHT offered probability of increasing organ-confined cancer(OCC; pathological stage pT2 or lower N0M0) in the following group, which contains (a) patients who had moderately differentiated adenocarcinoma in the biopsy specimen and T2b or lower diseases, and (b) those who had well differentiated adenocarcinoma, T2c diseases and PSA levels of 10 ng/ml or higher, referred to as "OCC suitable criteria". Of 156 patients, 51 (33%) met OCC suitable criteria. In those cases, the proportion of OCC in NHT group was significantly higher than that in surgery group (11/12 (92%) vs. 16/39 (41%), p = 0.002). NHT is useful for increasing OCC in patients who meet OCC suitable criteria.     

Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma

PURPOSE: To determine whether combination 5-fluorouracil, cisplatin, and interferon alfa, an active regimen in advanced esophageal cancer, is efficacious as induction therapy before esophagectomy. MATERIALS AND METHODS: Forty-four patients with potentially resectable esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma were entered into a phase I/II study of this chemotherapeutic regimen and concurrent external-beam radiotherapy before resection. The initial 16 patients were treated with prolonged-infusion 5-fluorouracil (300 mg/m2 on days 1 to 28), cisplatin (20 mg/m2 on days 1 to 5 and 24 to 28), interferon alfa (3 x 10(6) U/m2 intravenously on days 1 to 5 and 24 to 28; subcutaneous injection every other day on days 6 to 23), and radiation (4000 cGy). The subsequent 28 patients were treated over 21 days with two modifications: dose escalation of 5-fluorouracil (250 to 350 mg/m2) and double-fractionated radiotherapy to a total dose of 4500 cGy. RESULTS: Forty-one patients completed chemoradiotherapy and were evaluable for toxicity. Adverse events were substantial but tolerable, and most toxic episodes were hematologic and gastrointestinal. Three patients died, and one patient had progressive disease before resection. Of the 37 patients eligible for curative resection, 36 had all gross tumor removed. Thirty-three (80%) patients had a major pathologic response: 10 (24%) with no residual tumor and 23 with only microscopic residual tumor. Median survival for all patients was 27 months and for responders was 36 months. CONCLUSIONS: This combination regimen is active but yields results similar to those of other chemoradiotherapy phase II trials; therefore, the contribution of interferon alfa to treatment efficacy remains uncertain. The true worth of preoperative chemoradiotherapy is unknown pending results of phase III trials.     

Neoadjuvant intra-arterial chemotherapy based on chemosensitivity tests for locally invasive bladder cancer

We investigated the clinical usefulness of individualization of chemotherapeutic regimen in neoadjuvant intra-arterial chemotherapy for locally invasive bladder cancer. Anticancer drugs were selected according to the results of an in vitro chemosensitivity test (collagen matrix assay or succinic dehydrogenase inhibition test). Nine patients with locally invasive bladder cancer received 1 to 4 courses of neoadjuvant intra-arterial chemotherapy, followed by radical cystectomy. Histopathological responses in the cystectomized specimens were grade 3 in 3 cases, grade 2 in 2, grade 1b in 2 and no response in 2. Pathologically, a complete response and downstaging were observed in 3 and 4 cases, respectively. Seven of the 9 patients were alive no evidence of disease with a mean follow-up period of 38.9 months, whereas 2 patients died of metastasis within 2 years. Six of the 7 patients who showed a complete response or down staging have been free of recurrence. These findings suggest that our chemotherapeutic strategy may improve the prognosis for locally invasive bladder cancer.     

Influence of neoadjuvant treatment on bladder infiltrating tumors treated with radical cystectomy

Retrospective study of 107 patients diagnosed with infiltrant tumour of the bladder in stage T3-T4 N0-N1, treated with radical surgery. Eighty-four (84) received neoadjuvant therapy with radio- and/or chemotherapy. The neoadjuvant treatment was seen to provide significantly better survival, but the specific type of neoadjuvant treatment appears to have no influence. The multivariate study evidenced that the two most influential variables for survival are the complementary treatment and the clinical stage.