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PubMed1988

[Chemotherapy of soft tissue tumors].

The use of chemotherapy in the treatment of patients with advanced soft tissue sarcoma and as adjuvant and neoadjuvant therapy is reviewed. In advanced disease a response rate of up to 35% can be achieved with combination chemotherapy, but these are mainly partial remissions; few complete remissions are attained. The median survival for patients in partial remission is 2 years. The most active cytotoxic drug is adriamycin, with a remission rate of 30%. The addition of dacarbazine can increase the remission rate; however, this has no significant impact on survival and the toxicity is more pronounced. The activity of neoadjuvant or adjuvant chemotherapy is still controversial. Some studies indicate a positive effect on disease-free or overall survival with adriamycin-containing regimens. Other studies have not confirmed these results. More controlled trials with adequate numbers of patients stratified for tumor subtype, tumor localization and grading are needed to define the value of adjuvant or neoadjuvant chemotherapy in soft tissue sarcomas. Optimal interdisciplinary treatment can only be realized at specialized centers.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

The role of preoperative radiotherapy in nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery.

PURPOSE: To assess the role of preoperative radiotherapy in patients with nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery and to compare the response of neoadjuvant therapies, local control, and survival with the literature results. METHODS AND MATERIALS: Forty-six patients with osteosarcoma of the limbs who were treated within a limb salvage protocol including preoperative radiotherapy and chemotherapy between 1987 and 2002, were retrospectively analyzed. Median age was 17 years (range, 14-66 years). Treatment was started with neoadjuvant chemotherapy. Cisplatin, epidoxorubicin, ifosfamide, and methotrexate were used in different combinations. Preoperative radiotherapy was applied, usually between the second and third cycle of chemotherapy. Radiotherapy was given (35 Gy in 10 fractions) to 44 patients. Two patients were treated with 46 Gy at 2 Gy/day. Definitive surgery was administered after the third course of chemotherapy. Chemotherapy was complete 6 courses postsurgery. RESULTS: Median follow-up time was 44 months (range, 2-154 months). Forty-four patients had limb-sparing surgery, whereas 2 had amputation. Tumor necrosis rate was >/=90% in 87% of the patients (Huvos Grade 3-4). Two patients had local failures, and 26 patients (56.5%) had distant metastases. The 5-year local control and overall survival rates were 97.5% and 48.4%, respectively. On univariate analysis, age </=18 years, Huvos Grade 4, lower-extremity localization, and surgery within 1 month significantly survived better than the others. On multivariate analysis, Huvos grade (p = 0.01), age (p = 0.01), interval between neoadjuvant chemotherapy and surgery (p = 0.02), and extremity localization (p = 0.02) were significant prognostic factors for actuarial survival. Severe complication developed in 20% of the patients. CONCLUSION: Preoperative radiotherapy helps to increase the chance of extremity-sparing surgery with good local control and necrosis rate when combined with chemotherapy.

Adolescent↗

PubMed2006

Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer.

PURPOSE: To investigate the relationship of hypoxia-inducible factor-1alpha (HIF-1alpha) tumor expression in predicting the response to epirubicin and disease-free survival (DFS) in patients with breast cancer enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. EXPERIMENTAL DESIGN: The expression of HIF-1alpha was assessed by immunohistochemistry in 187 patients with T(2-4) N(0-1) breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. All patients postoperatively received four cycles of the four weekly i.v. CMF regimen (cyclophosphamide, methotrexate, and 5-fluorouracil). Patients with estrogen receptor (ER)-positive primary tumors also underwent 5 years of treatment with adjuvant tamoxifen. Carbonic anhydrase IX (CAIX) was also scored as a marker of HIF activity. RESULTS: Overall response to therapy progressively decreased with increasing tumor HIF-1alpha (P < 0.05), and HIF-1alpha was an independent predictor of response (P < 0.048). HIF-1alpha expression was also associated with a significantly shorter DFS (P < 0.02) in all patients and in ER-positive but not in ER-negative patients. Furthermore, CAIX positivity conferred a significantly shorter DFS (P = 0.02) compared with CAIX-negative tumors in patients with HIF-1alpha-negative tumors. CONCLUSIONS: HIF-1alpha expression in patients with breast cancer is a marker of poor therapy response and outcome, especially in ER-positive patients. The combination of two hypoxia markers has greater utility than assessing just one, and patients with hypoxia markers in their tumors may be suitable for administration of drugs that reduce HIF-1alpha expression and increase oxygen delivery to the tumor bed before starting neoadjuvant therapies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Concurrent docetaxel and thoracic radiation in non-small-cell lung cancer.

Locally advanced (stages IIIA and IIIB) non-small-cell lung cancer (NSCLC) represents approximately 25% of new cases of NSCLC diagnosed annually. The treatment strategy for these patients involves combined-modality therapy with chemotherapy and thoracic radiation. Furthermore, a subset of patients with stage IIIA disease undergo surgical resection. Docetaxel is a chemotherapy agent with activity in both first- and second-line treatment of patients with advanced NSCLC. Several recent studies have also incorporated docetaxel in the treatment of patients with stage III NSCLC as neoadjuvant therapy, alone or in combination with cisplatin or carboplatin and thoracic radiation. Docetaxel has also been used as consolidation therapy. This review will summarize the data to date on the use of docetaxel and thoracic radiation in the treatment of patients with stage III NSCLC.

Journal Article↗

PubMed1990

Neoadjuvant chemotherapy with cisplatinum and 5-fluorouracil in advanced head and neck cancer.

Forty-one patients affected by solid tumors of the head and neck were treated with neoadjuvant therapy before radiotherapy or surgery. All patients received therapy with cisplatinum 100 mg/m2 day 1 and 5-fluorouracil 1000 mg/day for days 1-5 by continuous infusion with a portable chronoinfusor. After three cycles, we observed an objective response in 34/41 patients (82.9%), with 9 (21.9%) complete remissions and 25 (61%) partial remissions. The main side effects were few and controllable. In our experience, neoadjuvant chemotherapy was able to induce a significant remission in 4/5 of patients, with better prospects for subsequent surgery and/or radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Role of adjuvant therapy in resected stage II/IIIA non-small-cell lung cancer.

The role of adjuvant therapy following complete resection of node-positive (stage II/IIIA) non-small-cell lung cancer remains controversial. Five-year survival rates in pathologic stage II disease range from 30% to 50% and in resected stage IIIA disease from 10% to 30%. The majority of recurrences following surgery are distant metastases. This two-part review, which will conclude in the January 2002 issue, analyzes the role of adjuvant therapy in this setting, using an evidence-based approach and focusing primarily on randomized trials and meta-analyses. The key variables in evaluating these studies are elucidated, ranging from the extent of mediastinal, systemic, and "molecular" staging to the quality of the adjuvant treatments administered. Some of the potential flaws inherent in meta-analyses are reviewed. To date, there is no convincing evidence that any therapy consistently improves survival in the adjuvant setting. Postoperative radiotherapy has been associated with a significant improvement in local control, particularly in patients with pathologic N2 disease. Chemotherapy should be offered to patients in appropriate clinical trials, and active phase III trials are reviewed. Future strategies include novel chemotherapy, methods to reduce toxicity, the emerging role of neoadjuvant therapy, and the promise of new biologic agents.

Carcinoma, Non-Small-Cell Lung↗

PubMed2002

Role of adjuvant therapy in resected stage II/IIIA non-small-cell lung cancer.

The role of adjuvant therapy following complete resection of node-positive (stage II/IIIA) non-small-cell lung cancer remains controversial. Five-year survival rates in pathologic stage II disease range from 30% to 50% and in resected stage IIIA disease from 10% to 30%. The majority of recurrences following surgery are distant metastases. This two-part review, which began in the December 2001 issue, analyzes the role of adjuvant therapy in this setting, using an evidence-based approach and focusing primarily on randomized trials and meta-analyses. The key variables in evaluating these studies are elucidated, ranging from the extent of mediastinal, systemic, and "molecular" staging to the quality of the adjuvant treatments administered. Some of the potential flaws inherent in meta-analyses are reviewed. To date, there is no convincing evidence that any therapy consistently improves survival in the adjuvant setting. Postoperative radiotherapy has been associated with a significant improvement in local control, particularly in patients with pathologic N2 disease. Chemotherapy should be offered to patients on appropriate clinical trials, and active phase III trials are reviewed. Future strategies include novel chemotherapy, methods to reduce toxicity, the emerging role of neoadjuvant therapy, and the promise of new biologic agents.

Carcinoma, Non-Small-Cell Lung↗

PubMedDate not supplied

Combined modality therapy for non-small cell lung carcinoma.

Combined modality therapy is frequently used to treat non-small cell lung carcinoma (NSCLC). Surgical resection is the mainstay of treatment for Stages I and II NSCLC. Little evidence supports the use of adjuvant therapy In patients with Stage I NSCLC. Adjuvant radiotherapy to the chest after resection for Stage II and IIIA NSCLC remains controversial but may be appropriate for many patients with resected Stage IIIA disease or inadequately pathologically staged II disease. For Stage IIIA NSCLC, surgery appears suboptimal, though no other single modality appears superior. Recent studies of neoadjuvant therapy for Stage IIIA NSCLC yielded promising results. The standard of care for Stage III unresectable NSCLC and strategies to improve local-regional control in Stage III NSCLC are discussed, as are the importance of toxicity protection with chemoradiation and the potential utility of prophylactic cranial irradiation for preventing brain relapse. Targeted therapies appear promising, and expedited evaluation in Stage III NSCLC is warranted.

Carcinoma, Non-Small-Cell Lung↗

PubMed1998

Review of cost-effectiveness assessments of chemotherapy in adjuvant and advanced breast cancer.

Economic assessments of treatment alternatives in breast cancer have been predominantly ones addressing the role and type of adjuvant therapy. These assessments have shown that the effectiveness of the intervention drives the cost-effectiveness results. Other key factors were the relative risk of recurrence, the time frame considered and only minimally the costs of the intervention. Assessments in advanced breast cancer are few in parallel with the limited number of phase III trials. Future assessments should address neoadjuvant therapy, high-dose adjuvant therapy and agents that alter disease associated complications agents such as biphosphonates.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Assessment of clinical impact of endoscopic ultrasound on rectal cancer.

INTRODUCTION: Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is the most accurate imaging modality for locoregional staging of rectal cancer. It remains unclear whether this technology impacts the clinical outcome of patients with this malignancy. The aim of this study was to assess the impact of EUS FNA by comparing the clinical outcomes of patients with rectal cancer before and after the introduction of EUS in our institution. METHODS: Outcomes of patients with de novo nonmetastatic rectal cancer seen in 1999 without EUS evaluation (non-EUS control group) were compared to patients evaluated in 2000/2001 with EUS FNA (EUS group). RESULTS: Outcomes of 68 (non-EUS control group) and 73 (EUS group) patients with nonmetastatic rectal cancer were compared. Among patients with advanced T or N stage, adjuvant therapy was administered to 45 patients (84.9%; preoperative to 31 (58.5%) patients and postoperative to 14 (26.4%)) in the EUS group; adjuvant therapy was administered to 37 patients (78.7%; preoperative to 7 (14.9%) patients and postoperative to 30 (63.8%)) in the non-EUS group. Cox proportional hazards demonstrated EUS FNA to be associated with reduced tumor recurrence risk, hazard ratio, 0.72 (95% CI: 0.52-0.97, p= 0.03). CONCLUSIONS: EUS staging of rectal cancer appears to facilitate appropriate employment of preoperative neoadjuvant therapy in those patients with advanced disease. EUS use is associated with a recurrence-free survival advantage in patients, supporting its routine use in rectal cancer staging.

Female↗

PubMed1988

Nonsurgical treatments for skin cancer: retinoids and alpha-interferon.

Retinoids, the natural and synthetic analogs of vitamin A, and alpha-interferon have been used effectively in the treatment of certain cutaneous premalignancies and malignancies. Retinoids have shown impressive activity against premalignant disorders of the skin (actinic keratoses, keratoacanthoma, epidermodysplasia verruciformis) and of other epithelial sites (oral leukoplakia, cervical dysplasia). In established basal cell skin cancers, topical retinoid treatment has produced a complete response rate of 33%, and systemic retinoids have produced an objective response rate of 51%. In advanced squamous cell skin cancers, systemic retinoids have produced a response rate of over 70%. Intralesional alpha-interferon has produced impressive responses and systemic alpha-interferon has produced a 50% objective response rate in basal and squamous cell carcinoma. Retinoid therapy and alpha-interferon have produced modest overall results in melanoma, although striking individual responses have been reported. In cutaneous T-cell lymphoma, which is notably refractory to chemotherapy, retinoids and alpha-interferon have produced responses in 60%+ and 70%+ of cases, respectively. Retinoids and alpha-interferon, either alone or in combination, offer exciting prospects for primary and neoadjuvant therapy for advanced malignancy. Retinoids also show promise as relatively nontoxic preventive and adjuvant therapy. Researchers should focus on integrating these drugs with other biological response modifiers, differentiation agents, and cytotoxic drugs for treating advanced malignancy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

The invasive staging and the role of complete resection in the surgical treatment of NSCLC.

Years of debates couldn't solve the discussion between the NSCLC assessment founded on CT scan and mediastinoscopy as in the Western countries and the refined extensive bronchoscopy, CT imaging and exploratory thoracotomy as practiced in Japan. Recently, the clinical onset of combined therapy protocols, the recognised value of the intrathoracic staging (also in the West) and survival rates in the earlier N2 disease moved towards change this steady situation. The role of complete resection in N2 NSCLC is therefore debated from the preoperative assessment to survival results in resected cases. Accuracy of CT scan and cervical mediastinoscopy is discussed also in the light of neoadjuvant therapy. The clinical value of intrathoracic staging is improved by Japanese experiences while a rationale assessment of Complete/Incomplete Resections is defined. Moreover, technical details of intraoperative recognition are cleared.

Carcinoma, Non-Small-Cell Lung↗

PubMed1998

[Is preoperative chemotherapy in locally advanced non-small-cell bronchial carcinoma of value?].

Although surgeons are able to resect completely locally advanced non-small cell lung cancer with mediastinal lymph node involvement (stage IIIA), the majority of patients succumb from metastatic disease. Therefore, neoadjuvant therapy was introduced in the management of this disease in order to eradicate distant metastases at an early stage. Phase II trials with preoperative chemotherapy in stage IIIA patients have shown that the pathological response (amount of tumour necrosis) and the clearance of mediastinal lymph node correlate with a better survival and is the best predictor for eradication of distant metastases. Indeed, three small randomised phase III studies have demonstrated a survival advantage for preoperative chemotherapy compared to surgery alone. Further studies are required to determine the best neoadjuvant regimen inducing the largest amount of tumour necrosis.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Evolving management and outcome of esophageal cancer with airway involvement.

BACKGROUND: Esophageal cancer with airway involvement, including patients with esophagorespiratory fistula (ERF), has been associated with a poor prognosis. Multimodality treatment, self-expanding metal stents, and improved supportive therapy may be impacting outcome in these patients. There is concern for the development of ERF during therapy. METHODS: We retrospectively studied 74 consecutive male patients at a single institution presenting between 1/85 to 12/98 with bronchoscopic, endoscopic or radiographic confirmation of airway involvement with esophageal cancer, including 35 patients with ERF. Comparison was made between the first 35 patients (group I) and the last 39 patients (group II) with regard to antineoplastic therapy, stent placement, and survival. RESULTS: Treatment in group I included supportive care in 17 of 35 patients, plastic stent in 7 of 35 patients, and radiation or chemotherapy in 9 of 35 patients. In group II, radiation or chemotherapy was offered to 33 patients, and self-expanding metal stents were placed in 10 of 39 patients. Surgical resection was possible after neoadjuvant therapy in 13 of 39 patients in group II, including 2 initially presenting with ERF. Median survival in group I was 16 weeks and in group II was 37 weeks. Comparison of Kaplan-Meier survival estimates using log rank testing demonstrated improved survival in group II (p = 0.0026). Long-term survival in 4 group II patients initially presenting with ERF and receiving multimodality treatment was observed. Development of ERF during treatment occurred in 3 group II patients. Treatment failure was predominantly local in group I and local and distant in group II. CONCLUSIONS: More aggressive treatment may favorably influence outcome in esophageal cancer with airway invasion. Long-term survival and the development of ERF during therapy occurred at similar rates.

Adenocarcinoma↗

PubMed2000

Neoadjuvant and adjuvant therapy for operable hepatocellular carcinoma.

OBJECTIVES: To determine the efficacy and adverse effects of different neoadjuvant and adjuvant therapies compared to surgery alone or surgery and placebo/supportive therapy when given to improve relapse and survival rates for operable hepatocellular carcinoma. SEARCH STRATEGY: Electronic databases, conference proceedings, bibliographies of identified publications. SELECTION CRITERIA: All truly randomised and quasi-randomised clinical trials that compared hepatocellular carcinoma patients who were given and not given neoadjuvant/adjuvant therapy as a supplement to curative liver resection. DATA COLLECTION AND ANALYSIS: Study data was extracted independently by two reviewers and discrepancies were resolved by consensus. A total of eight randomised controlled clinical trials were identified, totaling 548 randomised patients. Seven of the eight trials reported survival and disease-free survival curves and the results of hypothesis testing (log-rank test). The remaining trial reported only the mean survival times. None reported the hazard ratio and only one did a sample size calculation. The survival and disease-free survival curves were compared using their one, two and three-year survival rates, median survival times and the result of the hypothesis tests. MAIN RESULTS: The size of the randomised clinical trials ranged from 40 to 115 subjects. Both preoperative (neoadjuvant) and postoperative (adjuvant), systemic and locoregional (+/- embolization), chemo- and immunotherapy interventions were tested. None were comparable in terms of both treatment regimen and participants selected, so no pooling was done. Only one regimen using preoperative transcatheter arterial chemoembolization with doxorubicin was approximately duplicated. Seven of the eight trials reported no survival benefit from adjuvant therapy. Only one trial reported a statistically significant difference for survival and disease-free survival for the treatment arm, but the results of both its arms were very poor when compared to other studies. Two of the trials that did not report any absolute survival advantage reported statistically significant differences in disease-free survival. Five of the eight trials did not perform intention-to-treat analysis. The highest toxicity rate was in a trial using oral 1-hexylcarbamoyl 5-fluorouracil which resulted in 12 out of 38 subjects stopping because of adverse events. REVIEWER'S CONCLUSIONS: There is no evidence for efficacy of any of the adjuvant protocols reviewed. In order to detect a realistic treatment advantage, larger trials will have to be conducted.

Antineoplastic Agents↗

PubMed1990

Influence of chemotherapy on perioperative complications in limb salvage surgery for bone tumors.

From 1970 to 1986, 304 patients underwent limb salvage resections for 271 malignant and 33 benign tumors of the extremities. Reconstruction was with a prosthesis or nonbiologic spacer. Nonmechanical complications were analyzed to determine the influence of the site and method of reconstruction and the use of chemotherapy on their incidence and severity. There were 82 shoulder resections, 53 proximal femur resections, and 169 knee resections. No chemotherapy was used in 115 patients; neoadjuvant therapy was used in 128 patients and adjuvant therapy was used in 61. There were 120 complications. The most common complication was infection (36 of 304 patients; 11.8%), which led to amputation in eight patients. Resections about the knee led to more complications than the other sites, particularly if reconstructed with a large cement spacer. Patients who did not receive any chemotherapy had a 25.2% (29 of 115) incidence of complications and those who received adjuvant treatment had a 32.8% (20 of 61) incidence. This compares with a 55.4% (71 of 128) incidence in the neoadjuvant group. After neoadjuvant chemotherapy, reconstruction with an uncemented prosthesis led to the fewest complications.

Antineoplastic Agents↗

PubMed2000

Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study.

BACKGROUND: The last two decades have seen changes in the prevalence, histologic type, and management algorithms for patients with esophageal cancer. The purpose of this study was to evaluate the presentation, stage distribution, and treatment of patients with esophageal cancer using the National Cancer Database of the American College of Surgeons. STUDY DESIGN: Consecutively accessed patients (n = 5,044) with esophageal cancer from 828 hospitals during 1994 were evaluated in 1997 for case mix, diagnostic tests, and treatment modalities. RESULTS: The mean age of patients was 67.3 years with a male to female ratio of 3:1; non-Hispanic Caucasians made up most patients. Only 16.6% reported no tobacco use. Dysphagia (74%), weight loss (57.3%), gastrointestinal reflux (20.5%), odynophagia (16.6%), and dyspnea (12.1%) were the most common symptoms. Approximately 50% of patients had the tumor in the lower third of the esophagus. Of all patients, 51.6% had squamous cell histology and 41.9% had adenocarcinoma. Barrett's esophagus occurred in 777 patients, or 39% of those with adenocarcinoma. Of those patients that underwent surgery initially, pathology revealed stage I (13.3%), II (34.7%), III (35.7%), and IV (12.3%) disease. For patients with various stages of squamous cell cancer, radiation therapy plus chemotherapy were the most common treatment modalities (39.5%) compared with surgery plus adjuvant therapy (13.2%). For patients with adenocarcinoma, surgery plus adjuvant therapy were the most common treatment methods. Disease-specific overall survival at 1 year was 43%, ranging from 70% to 18% from stages I to IV. CONCLUSIONS: Cancer of the esophagus shows an increasing occurrence of adenocarcinoma in the lower third of the esophagus and is frequently associated with Barrett's esophagus. Choice of treatment was influenced by tumor histology and tumor site. Multimodality (neoadjuvant) therapy was the most common treatment method for patients with esophageal adenocarcinoma. The use of multimodality treatment did not appear to increase postoperative morbidity.

Aged↗

PubMed2003

Results of surgical therapy in patients with Barrett's adenocarcinoma.

The incidence of adenocarcinoma arising from Barrett's esophagus is dramatically increasing in Western countries. The purpose of this study was to report our experience in the surgical management of these patients. Between November 1992 and December 2000, 330 consecutive patients with adenocarcinoma of the esophagogastric junction were observed in our institution. Of these, 105 (31.8%) had Barrett's carcinoma. In 12 individuals (11.4%) adenocarcinoma was discovered during endoscopic surveillance for Barrett's esophagus. Twelve patients with doubtful cleavage planes at preoperative investigation were treated with neoadjuvant chemotherapy. Overall, 80 patients (76.2%) underwent esophagectomy without operative mortality. The Ivor Lewis approach was used in 70 patients; of these, 31 underwent extended mediastinal lymph node dissection. Seventy-four patients (92.5%) had R0 resection. The overall 5-year survival rate was 48%. Survival was significantly associated with stage, lymph node status, and completeness of resection. Early diagnosis remains the prerequisite for curative treatment of esophageal carcinoma. An extended mediastinal lymphadenectomy does not increase morbidity, allows precise tumor staging, and may prove effective in preventing local recurrences. Neoadjuvant therapy requires major improvement before it can be unconditionally recommended outside clinical trials.

Adenocarcinoma↗