Increase In 5-year Survival Research Articles

Docetaxel as neo-adjuvant therapy for radically treatable stage III non-small cell lung cancer: early results of an international phase III study

During the last decade, neo-adjuvant chemotherapy has shown the potential to improve the survival of patients with stage III non-small cell lung cancer (NSCLC) [1–3]. A meta-analysis performed by the Non-small Cell Lung Cancer Collaborative Group has demonstrated a small survival advantage for patients who had received cisplatin-based neo-adjuvant therapy before definitive radical radiotherapy [4]. In this analysis, neo-adjuvant therapy was associated with a 13% reduction in mortality and a 5% increase in 5-year survival. There is a clear rationale for using neo-adjuvant chemotherapy before definitive local treatment of NSCLC by improving delivery of the chemotherapeutic agent to the tumour site through an intact blood supply that has not been disrupted by prior surgery or radiotherapy. Initially unresectable tumours may be transformed into operable ones, and the frequent occult extra-thoracic micrometastases in patients with stage III NSCLC may be eradicated. This approach may also reduce the extent of surgical resection and improve the degree of local control achieved with radiotherapy. The significant toxicity associated with cisplatin has led to the evaluation of other agents, including docetaxel, for the neo-adjuvant treatment of NSCLC. Single-agent docetaxel has been shown to be active in NSCLC. Four phase II trials, involving a total of 180 patients with advanced or metastatic NSCLC, have demonstrated that first-line therapy with docetaxel is associated with an objective overall response rate of 30% and a median overall survival of 9 months [5–8]. Docetaxel is one of the several chemotherapeutic agents that have recently received approval, in the USA and Europe, for second-line treatment of locally advanced or metastatic NSCLC. In view of its encouraging activity in advanced NSCLC, docetaxel is currently being investigated in the neo-adjuvant setting.

Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review

Objectives. Combined androgen blockade with medical or surgical castration plus a nonsteroidal antiandrogen for metastatic prostate cancer has been the subject of 20 randomized trials. The findings range from no expected increase in survival in 17 studies to an estimated 3.7 to 7 months’ survival improvement noted in 3 studies. Most recently, a 1999 evidence report from the Agency for Healthcare Research and Quality and a 2000 overview from the Prostate Cancer Trialists Collaborative Group indicated that combined androgen blockade was associated with an approximately 3% to 5% increase in 5-year survival. We report herein a systematic review on combined androgen blockade performed by the Cochrane Collaborative Review Group on Prostate Diseases. Methods. Controlled trials that included a randomization of immediate nonsteroidal antiandrogens with castration versus castration alone for metastatic prostate cancer and provided information on survival were reviewed. Information on overall survival, toxicity, progression-free survival, cancer-specific survival, and type of nonsteroidal antiandrogen and castration therapies was abstracted by two independent reviewers. Results. Twenty trials (n = 6320 patients) were included. The pooled odds ratio (OR) for overall survival with combined androgen blockade was 1.03 (95% confidence interval [CI] 0.85 to 1.25; n = 4970 from 13 trials), 1.16 (95% CI 1.00 to 1.33; n = 5286 from 14 trials), and 1.29 (95% CI 1.11 to 1.50; n = 3550 from 7 trials) at 1, 2, and 5 years, respectively. Progression-free survival was improved at 1 year (OR = 1.38; 95% CI 1.15 to 1.67; n = 2278 from 7 trials). Cancer-specific survival was improved at 5 years (OR = 1.58; 95% CI 1.05 to 2.37; n = 781 from 2 trials). When analysis was limited to studies identified as being of high quality, the pooled OR for overall survival progressively increased but was not significant at any follow-up interval. Conclusions. We find that there is a 5% improvement in the percentage of men surviving at 5 years (30% vs. 25%) with combined androgen blockade with nonsteroidal antiandrogens as well as improvements in progression-free survival at 1 year. Appropriate patients with metastatic prostate cancer should be informed of the potential benefits, toxicities, and out-of-pocket expenditures.

Are Increasing 5-Year Survival Rates Evidence of Success Against Cancer?

Increased 5-year survival for cancer patients is generally inferred to mean that cancer treatment has improved and that fewer patients die of cancer. Increased 5-year survival, however, may also reflect changes in diagnosis: finding more people with early-stage cancer, including some who would never have become symptomatic from their cancer. To determine the relationship over time between 5-year cancer survival and 2 other measures of cancer burden, mortality and incidence. Using population-based statistics reported by the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we calculated the change in 5-year survival from 1950 to 1995 for the 20 most common solid tumor types. Using the tumor as the unit of analysis, we correlated changes in 5-year survival with changes in mortality and incidence. The association between changes in 5-year survival and changes in mortality and incidence measured using simple correlation coefficients (Pearson and Spearman). From 1950 to 1995, there was an increase in 5-year survival for each of the 20 tumor types. The absolute increase in 5-year survival ranged from 3% (pancreatic cancer) to 50% (prostate cancer). During the same period, mortality rates declined for 12 types of cancer and increased for the remaining 8 types. There was little correlation between the change in 5-year survival for a specific tumor and the change in tumor-related mortality (Pearson r=.00; Spearman r=-.07). On the other hand, the change in 5-year survival was positively correlated with the change in the tumor incidence rate (Pearson r=+. 49; Spearman r=+.37). Although 5-year survival is a valid measure for comparing cancer therapies in a randomized trial, our analysis shows that changes in 5-year survival over time bear little relationship to changes in cancer mortality. Instead, they appear primarily related to changing patterns of diagnosis. JAMA. 2000.

Il Trattamento Chirurgico Resettivo Del Carcinoma Pancreatico

Aims and background Surgical resection offers the only potential cure for pancreatic carcinoma. Although the overall prognosis remains a dismal, several recent series have reported an encouraging increase in 5-year survival after resection, ex-ceding 20%. As the reasons for this improvement are not clearly understood, numerous clinico-pathological parameters (demographic, intraoperative and histopatologic factors) have been investigated to evaluate their role in predicting long term survival. In this single-institution study, immediate and long-term outcome after pancreatic resection in patients with pancreatic adenocarcinoma was retrospectively evaluated, focusing attention on the possible impact of different clinico-pathologic factors on long-term survival. Methods Sixty-six patients with a confirmed histologic diagnosis of adenocarcinoma of the pancreas, treated by pancreatic resection at the Department of Surgery of the Catholic University of Rome in the years 1988-1997, were retrospectively analyzed. Morbidity and survival data were reviewed and potential prognostic factors were compared statistically by univariate analysis. Results There was no postoperative mortality. Twenty-five patients (38%) developed major operative complications. Pancreatic fistula was the most common complication, and occurred in 7 patients (11%). The actuarial overall and disease-specific survival for all 66 patients were respectively 58% and 59% at 1 year, 27% and 31% at 3 years, and 13% and 20% at 5 years, with a median survival time of 13.4 months. Nodal status was the only single factor significantly affecting survival by univariate analysis. The 3-and 5-year survival rates were respectively 35% and 19% for node-negative patients and 7% and 0% for node-positive patients (P = .04). A positive correlation with improved survival, even if not of statistical significance, was shown for other pathologic or intraoperative factors. Among the former, 5-year survival rates were better for patients with negative resection margins as compared to patients with positive margins (12% vs 7%, P = ns). Among the latter, a better actuarial 5-year survival rate was shown for patients with shorter operative time (<4 hours, 21% survival vs >4 hours 5%, P = ns) and for patients that received fewer transfusions (0-2 blood units, 14% survival vs 3 or more blood units, 0%; P = ns). Age, gender, tumor diameter and tumor grading showed no influence on survival in this series. Conclusions Our series confirmed that nodal status is the strongest independent predictor of survival. Limited intraoperative transfusion, reduced operative time and clear margins could also yeald a prognostic significance, and require further confirmation in larger series.

Multimodal therapy of colon carcinoma

A large variety of immunological and cytotoxic adjuvant treatment concepts and application routes have been observed to be effective in colon cancer by randomized trials during the past three decades. Presently adjuvant 5-fluorouracil based chemotherapy is favoured for patients with lymph node metastases (UICC stage III), since this treatment was associated with a 5-10% increase in 5-year survival. Uncertainty persists regarding the optimal use of adjuvant treatment, since marked differences in prognosis have been recognized within stage III and because the impact of surgical treatment on long-term survival has not been thoroughly controlled for in past trials. Current and future studies will have to determine precisely which patients will benefit most from adjuvant treatment and which combination of surgical and adjuvant treatment will be most effective.

Five‐year survival for cisplatin‐based chemotherapy versus single‐agent melphalan in patients with advanced ovarian cancer and optimal debulking surgery

The purpose of this study was to evaluate 5-year survival and 5-year progression-free survival in previously untreated patients with advanced ovarian cancer treated with single-agent melphalan in which very few patients underwent optimal debulking surgery (less than 2 cm residual) as compared with the patients treated with Cisplatin-based chemotherapy in which most patients underwent optimal debulking surgery. Significant increases in 5-year survival and 5-year progression-free survival were noted as we changed from the melphalan trial, in which only 14% underwent optimal debulking surgery, to PAC-H, in which 57% and the PAC trial in which 90%, respectively, underwent optimal debulking surgery. However, for those patients whose tumors were optimally debulked in the three trials, there were no statistically significant differences in median survival, median progression-free survival, 5-year survival, or 5-year progression-free survival in those patients treated with melphalan, PAC-H, or PAC. Without optimal debulking surgery, Cisplatin-based multiagent chemotherapy offered a small survival advantage. These results are similar to that reported by Gruppo Interregionale Cooperativo Oncologico Ginecologia, in which survival curves were identical for all the subgroups of chemotherapy regimens for those patients with residual disease less than 2 cm at the onset of chemotherapy whether they received (1) cyclophosphamide; (2) cyclophosphamide and Adriamycin; (3) cyclophosphamide, Adriamycin, and Cisplatin; (4) cyclophosphamide, Adriamycin, and hexamethylmelamine; (5) Cisplatin and cyclophosphamide; (6) low-dose Cisplatin; (7) high-dose Cisplatin; or (8) carboplatin.

Cis-diamminedichloroplatinum II based combination chemotherapy for the control of extensive paraaortic lymph node metastasis in cervical cancer

A prospective study was carried out in nine consecutive patients with extensive paraaortic lymph node metastasis from locally advanced cervical cancer. Patients were treated with pelvic radiation and weekly cis-platinum during radiation followed by cis-platinum based combination chemotherapy given on a monthly basis. Three weeks after completion of pelvic radiation and weekly cis-platinum, and prior to monthly combination chemotherapy, pelvic examination confirmed a 100% local response rate: 78% complete and 32% partial response. All patients have been followed for ⩾1 year or until death and only 22% (2) are alive NED while 56% (5) are dead of cervical cancer and 22% (2) are alive with cervical cancer. Although there was a significant response to local pelvic tumor by pelvic radiation and weekly cis-platinum, it is concluded that this protocol would not result in a significant increase in 5-year survival for patients with extensive paraaortic lymph node metastasis, because of the inability to control disease outside of the radiated area.

Preoperative radiotherapy for adenocarcinoma of the rectosigmoid

Ninety-seven patients with adenocarcinoma of the rectosigmoid have been treated with high dose (5000-6000 rad) preoperative irradiation from 1960 through 1972 at the University of Oregon Health Sciences Center. Fifty-seven were initially clinically resectable and 40 were initially inoperable. Forty of the 57 initially clinically resectable patients had "curative" resections and are at risk for more than 5 years. An increase in 5-year survival (from 38% to 53%) and an absence of pelvic recurrence have occurred in those patients receiving preoperative irradiation and "curative" resection. Four of the 40 initially inoperable patients are alive without tumor. Three of the four survivors had irradiation and surgery; one had irradiation only. An additional four patients had no evidence of tumor at death. Tumor was totally sterilized by irradiation and nine patients and reduced to microfocal extent in an additional three of the 97 patients. Incidence of complications was no greater than has been reported in a surgical series from the same institution.