冬凌草单药及与化疗合用治疗食管癌205例

目的:观察冬凌草单药及与化疗合用治疗食管癌的临床疗效.方法:448例患者,均经病理细胞学和X线检查确诊为食管癌.其中早期癌76例,均采用冬凌草单药治疗.晚期癌372例,167例采用冬凌草单药治疗,205例采用冬凌草与化疗合用.结果:用冬凌草单药治疗早期食管癌患者3,5,10,13 a的生存率明显高于未治疗组(98.68% vs 51.52%,84.02% vs 28.62%,63.49% vs 11.45%,50.13% vs 8.59%;P<0.001).对于晚期食管癌,冬凌草联合化疗应用,其总有效率明显高于以PYM(BLM)为基础的单一化疗(66.82% vs 42.85%,P<0.01).冬凌草与化疗合用组与单一化疗对照组相比副作用基本相同,无明显差异(P>0.05).结论:对于早期食管癌患者,冬凌草能控制疾病发展延长生存时间;对于晚期食管癌患者,冬凌草能增强化疗的作用.     

Multimodality therapy in the treatment of lung cancer

Lung cancer is the leading cause of cancer death in the world, causing more than one million deaths each year. The incidence and mortality rates are highest in the United States and Europe and continue to increase in developing nations. Non-small cell lung cancer (NSCLC) accounts for 80 to 85% of all new cases of lung cancer. The majority of patients with NSCLC present with advanced disease at the time of diagnosis. Although the prognosis of advanced NSCLC is very poor, current chemotherapy combinations have been shown to improve 1-year survival and quality of life for these patients. Approximately one third of patients with NSCLC are diagnosed with locally advanced disease. Although cure rates are modest and variable in locally advanced NSCLC, multimodality therapy (chemotherapy in combination with surgery or radiotherapy) has resulted in statistically significant improvement in 5-year survival when compared with surgery or radiotherapy alone. Patients with early-stage NSCLC have the best long-term survival rates following surgical resection; however, systemic recurrences remain a problem in the majority of these patients. The rationale for treating patients with early-stage NSCLC with combined-modality therapy (chemotherapy and surgery) is compelling, and several randomized trials are currently in progress. Although progress has been slow, when we consider the recent advances in smoking prevention, smoking cessation, staging classification, imaging and diagnostic techniques, screening and therapeutic modalities, and multidisciplinary care, as well as in the understanding of the molecular pathogenesis of lung cancer, the future, in my opinion, is very promising.     

Peritoneal carcinomatosis of unknown primary site in women. A distinctive subset of adenocarcinoma

STUDY OBJECTIVE: To define the clinical features and results of systemic treatment in women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surfaces. DESIGN: Retrospective analysis of 18 patients treated at a single institution between 1978 and 1984. PATIENTS: All 18 women had abdominal carcinomatosis and had no primary site identified at laparotomy. Nine patients had limited residual tumor (maximal tumor diameter, 3 cm or less) after initial cytoreductive surgery, and 9 patients had extensive residual disease. INTERVENTIONS: In general, patients were treated according to standard guidelines for treatment of advanced ovarian carcinoma. All patients had initial laparotomy with attempted cytoreduction; of these 18 patients, 16 subsequently received cisplatin-based chemotherapy. Patients were restaged either clinically (10 patients) or with second-look surgery (8 patients). RESULTS: The median survival for all patients was 23 months. Five patients had complete response to chemotherapy, and three patients remain disease-free 41, 59, and 77 months after diagnosis. Patients with limited residual disease had longer median survival than did those with extensive residual disease (31 months compared with 11 months). CONCLUSIONS: Women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surface should be distinguished from other patients with adenocarcinoma of unknown primary site because they have a more indolent disease course, a higher response rate to systemic therapy, and a chance for long-term, disease-free survival after therapy. Although optimal treatment is undefined, we recommend that these patients be treated using the guidelines established for therapy of advanced ovarian carcinoma, including initial surgical cytoreduction followed by cisplatin-based combination chemotherapy.     

Gynaecological cancers in pregnancy

Cervical and ovarian cancers are the most common gynaecological cancers diagnosed during pregnancy. In early-stage cervical cancer during the first and at the beginning of the second trimester, the two main considerations for management of the patient are the tumour size (and stage) and nodal staging. MRI and laparoscopic lymphadenectomy are useful for clinicians planning a potentially conservative approach. The management of patients with locally advanced cervical disease is controversial and should be discussed on a case-by-case basis according to the tumour size, radiological findings, the term of pregnancy, and the patient's wishes. Different histological types of malignant ovarian diseases arise during pregnancy and their management depends on the diagnosis (histological subtypes, tumour differentiation, and nodal status), the tumour stage, and the trimester of the pregnancy. In patients with peritoneal spread or high-risk early-stage disease, neoadjuvant chemotherapy with pregnancy preservation could be appropriate.     

Second-line chemotherapy of stage III-IV ovarian carcinoma: a randomized comparison of melphalan to melphalan and hexamethylmelamine in patients with persistent disease after doxorubicin and cisplatin

A total of 205 women with stage III or IV ovarian cancer who had persistent disease after initial treatment with doxorubicin and cisplatin were randomized to receive melphalan (8 mg/m2 orally for 4 days) or the combination of melphalan (6 mg/m2 for 4 days) and hexamethylmelamine (120 mg/m2 for 14 days) every 4 weeks. Only one of 64 patients with measurable disease had an objective response. The major determinants of survival after randomization were the amount of residual disease after initial chemotherapy and the type of response to initial chemotherapy. There was no overall difference in survival between the two chemotherapy regimens, but the small group of patients whose disease progressed on initial chemotherapy survived significantly longer when treated with the two-drug combination. Neither of these regimens provided effective therapy for women whose disease was not eliminated by first-line treatment. However, the superior results obtained in one subgroup with the addition of hexamethylmelamine suggest that the place of this agent in treating ovarian cancer should be carefully evaluated.     

Ovarian cancer in the elderly

In Europe 58% of all female cancers occur in women older than 65 years. The incidence of ovarian cancer rises steadily with advancing age during adulthood and peaks in the 7th-8th decades of life. Age-specific analysis reveals that the incidence of and mortality rate from ovarian cancer are continuously increasing in the elderly population. Although more advanced stage at diagnosis seems to be one of the determinants of the worst prognosis of the elderly population, the majority of clinicians seem to be unprepared to treat elderly patients, and a great number of patients are under-treated for the fear of unacceptable side-effects, thus limiting their possibility of survival. Guidelines are clearly needed; including advice on whether to treat at all and whether standard surgery or chemotherapy is feasible in elderly patients with ovarian cancer. Research on MEDLINE using as keywords 'elderly and ovarian cancer' reveals few papers, which reported data in this field. Nonetheless, in this report we will focus on four basic aspects of ovarian cancer in the elderly: the most important factors affecting prognosis, the safety of surgical treatment in aged patients, optimal first and second line chemotherapy, and the use of supportive treatments to improve quality of life.     

Histologic grade in advanced ovarian cancer.

The histologic grade of epithelial ovarian tumors was found to be a major prognostic factor for survival in patients with advanced (stage III-IV) disease. In addition, a grading system based on cytologic detail (modified Broders' grades I-IV) identified groups with a differential response to chemotherapy. The overall improvement in survival observed with combination chemotherapy was related primarily to an increased survival of patients with grade II and III lesions. Although the survival of patients with grade I lesions was markedly better than for patients with grade IV lesions, in neither case was it influenced by the choice of single-agent or combination chemotherapy. In prospective clinical trials in advanced disease, modified Broders' grades should be included as a separate stratification factor.     

Effects of cancer treatment on the reproductive system

Many patients with Hodgkin's disease, acute leukemia, non-Hodgkin's lymphoma, testicular cancer, and other tumors now regularly achieve sustained clinical remissions and cures. Drugs used in the treatment of cancer have profound and often lasting effects on the testis and ovary. Germ cell production and endocrine function may both be altered with the magnitude of the effect related to the age, pubertal status, and menstrual status of the patient as well as to the particular drug, dosage, or combination administered. The primary testicular lesion caused by all antitumor agents studied thus far is depletion of the germinal epithelium lining the seminiferous tubules. Combination chemotherapy regimens that include alkylating agents produce germinal aplasia and permanent infertility in the majority of patients. The risk of ovarian injury following combination chemotherapy is clearly related to the age of the patient at the time of treatment. Overall, 40 to 50% of women treated with combination chemotherapy become amenorrheic, although the frequency of amenorrhea in women older than 35 years may be as high as 90%. Interventions to protect the gonads from the effects of chemotherapy have not yet been developed; thus, male patients should be offered an opportunity to store semen prior to treatment and all patients should be counseled concerning the potential gonadal toxicity of cancer chemotherapy.     

New aspects of adjuvant therapy in endometrial cancer: current standards and future directions

Endometrial cancer is one of the most common gynaecological cancers in western countries. Most women are diagnosed at an early stage of the disease and can be cured by surgery alone. In patients with poor prognostic factors or an advanced disease, the chance of progression-free survival and overall survival is greatly diminished. Adjuvant chemotherapy is effective for patients with advanced disease. The combination of doxorubicin and cisplatin achieves overall response rates ranging from 34 to 60%, and the addition of paclitaxel seems to improve the outcome of patients with advanced disease, but it induces a significantly higher toxicity. A Gynecologic Oncology Study Group phase-III study is currently exploring the triplet paclitaxel+doxorubicin+cisplatin plus G-CSF vs. the less toxic combination of paclitaxel+carboplatin. Ongoing and planned phase-III trials are evaluating newer combination chemotherapy regimens, a combination of irradiation and chemotherapy and the implementation of targeted therapies with the goal of improving the tumour control rate and quality of life.     

Non-surgical therapy for patients with advanced non-small cell lung cancer

Abstract Non-small cell lung cancer is the major cancer problem in the Western World. Treatment and prognosis are highly stage dependent, although overall only 5–10% of patients will be alive 5 years after diagnosis. Patients with early stage disease are treated with surgery alone. However, for patients with locally advanced disease there is increasing evidence that combined modality approaches, incorporating chemotherapy, radiotherapy and/or surgery result in modest improvements in survival. For patients with metastatic non-small cell lung cancer there is evidence from metaanalyses and randomised studies that chemotherapy results in improvements in both duration and quality of life. Despite these advances, there is substantial room for further improvement and therefore, wherever possible, patients should be enrolled in well designed clinical studies.     

Analysis of 96 patients with advanced ovarian carcinoma treated with high-dose chemotherapy and autologous stem cell transplantation

The purpose of this study was to identify characteristics significant to survival and progression-free survival in patients with advanced ovarian cancer receiving high-dose chemotherapy. In all, 96 patients received autologous stem cell transplantation. Regimens included paclitaxel with carboplatin (PC), topotecan, melphalan, cyclophosphamide (TMC) and cyclophosphamide, BCNU, thiotepa (CBT). At the time of transplantation, 43% of patients were in clinical CR, 34% were in clinical PR, 18% had progressive disease and 5% had stable disease. There were no treatment-related deaths. The 6-year survival by Kaplan-Meier was 38%. For patients who received transplantation for remission consolidation, the 6-year survival was 53% with a PFS of 29%. On univariate analysis, the CBT regimen, clear cell histology and disease status other than CR prior to treatment were statistically significant adverse prognostic factors. This analysis has demonstrated that patients in clinical remission are most likely to benefit from autologous transplantation, with the exception of patients with clear cell histology. The TMC combination appeared to be superior to the PC and CBT combinations. Comparative studies of different consolidation approaches will be necessary to determine if autologous transplantation is the preferred treatment for this patient population.     

Ovarian cancer

The standard initial management of epithelial ovarian cancer consists of surgical staging, operative tumour debulking including total abdominal hysterectomy and bilateral salpingo-oophorectomy, and administration of six cycles of intravenous chemotherapy with carboplatin and paclitaxel. Extensive and largely retrospective experience has shown that optimum surgical debulking to leave residual tumour deposits that are less than 1 cm in size is associated with improved patient outcomes. However, 75% of patients present with advanced (stage III or IV) disease and, although more than 80% of these women benefit from first-line therapy, tumour recurrence occurs in almost all these patients at a median of 15 months from diagnosis. Second-line treatments can improve survival and quality of life but are not curative. Advances in screening and understanding of molecular pathogenesis of ovarian cancer and development of novel targeted therapies (eg, bevacizumab) and practical intraperitoneal techniques for drug delivery are most likely to improve patient outcomes.     

Adjuvant Chemotherapy for Early-Stage Non-small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related mortality in the developed world. Non-small cell lung cancer (NSCLC) represents 85% of cases of lung cancer, and patients have a poor 5-year survival rate. Approximately one third of NSCLC patients present with early-stage disease that is amenable to potentially curative resection and multimodality therapy. Several randomized trials now have confirmed the survival benefit with adjuvant platinum-based chemotherapy, as seen in the 1995 meta-analysis from the NSCLC Collaborative Group. The International Adjuvant Lung Cancer Collaborative Group Trial demonstrated a 4.5% improvement in survival for patients with stage I to III NSCLC. Studies from Japan have reported an improvement of 15.4% in the 5-year survival rate among patients with T1N0 disease after they had received adjuvant therapy with a combination of platinum and uracil-tegafur, and an improvement in the 5-year survival of 11% rate favoring chemotherapy with uracil-tegafur in a subgroup analysis of patients with T2N0 disease. Two recently published meta-analyses have estimated a relative risk reduction in mortality of 11 to 13% at 5 years. Significant improvement in the long-term survival rate has been demonstrated for patients with stage IB and II disease by the Cancer and Leukemia Group B 9633 trial (4-year survival rate, 12%) and the The National Cancer Institute of Canada Clinical Trials Group BR.10 trial (5-year survival rate, 15%; risk reduction for recurrence, 40%). Thus, there is compelling evidence to now recommend adjuvant platinum-based combination chemotherapy for patients after resection of early-stage NSCLC.     

Should intraperitoneal chemotherapy be considered as standard first-line treatment in advanced stage ovarian cancer?

Current standard therapy for patients with advanced stage epithelial ovarian cancer is cytoreductive surgery followed by combination chemotherapy with paclitaxel and carboplatin. Intraperitoneal (IP) chemotherapy has demonstrated improved outcome compared to standard intravenous treatment in three large randomized phase III trials and confirmed by Cochrane meta-analysis. Although compelling evidence suggests that IP therapy provides survival benefit in a selected group of ovarian cancer patients, it remains unclear which group of patients will really benefit from IP therapy, which is the optimal drug, dose and combination, and what is the real benefit of IP treatment alone. Other concerns about IP therapy are difficulties in completing the assigned treatment and management of its pattern of toxic side-effects. Today, IP chemotherapy has yet to gain a role as standard first-line treatment in advanced stage ovarian cancer. In the near future, efforts should aim at developing an effective IP regimen and research undertaken for a better understanding of the peritoneal environment.     

Gemcitabine: current role and future options in the treatment of ovarian cancer

Epithelial ovarian cancer is the gynecological malignancy with the highest mortality. The standard therapeutic approach for patients with advanced-stage epithelial ovarian cancer has been cytoreductive surgery followed by combination chemotherapy. Despite improvements in outcome via carboplatin/paclitaxel based chemotherapy, 30% of patients with ovarian cancer fail to respond to primary therapy; moreover, 55-75% of responders relapse within 1 or 2 years from the end of primary treatment and die of the disease within 5 years from their initial diagnosis. Gemcitabine has been shown to be active as a single agent and in combination with other drugs, including carboplatin and paclitaxel, in the treatment of patients with recurrent ovarian cancer. It is currently under evaluation in new combinations for initial therapy in ovarian cancer patients.     

High-dose melphalan-based chemotherapy and autologous stem cell transplantation after second look laparotomy in patients with chemosensitive advanced ovarian carcinoma: long-term results

The importance of dose intensity has been suggested in ovarian carcinoma. We retrospectively evaluated the long-term results of melphalan-based high-dose chemotherapy (HDC) with hematopoietic rescue in a unicentric series of 33 patients with advanced ovarian cancer sensitive to first-line chemotherapy. Before HDC, treatment with debulking surgery and platinum-based chemotherapy was followed by second-look operation (SLO). HDC consisted of melphalan (n = 8), melphalan and cyclophosphamide (n = 9), or melphalan, etoposide and carboplatinum (n = 16). Toxicity was mainly hematological. One death occurred from infection during aplasia. With a median follow-up of 60 months after intensification, the 5-year progression-free survival (PFS) rate was 29% and the 5-year overall survival (OS) rate was 45%. Survival differed significantly according to tumor status at SLO. Women with microscopic or macroscopic disease at SLO, ie with a pathological partial response to first-line therapy (PPR), had survivals of 7% at 5 years, similar to other salvage therapies. Better results were obtained in the 20 women with a complete pathological response (PCR) at SLO with 43% 5-year PFS (median, 51 months) and 75% 5-year OS (median not reached). In conclusion, melphalan-based HDC with hematopoietic rescue had an acceptable toxicity in patients with chemosensitive advanced ovarian cancer. In situations of salvage therapy for patients in PPR, this treatment was not effective in long-term analysis. On the contrary, long-term results were favorable in patients with PCR, suggesting further prospective randomized studies comparing HDC and other consolidation treatments should be undertaken in this particular situation.     

Phase II trial of ifosfamide and cisplatinum in advanced ovarian cancer

To evaluate the efficacy of systemic ifosfamide, cisplatin (CDDP) combination as first line treatment followed by intraperitoneal (IP) chemotherapy with carboplatin (CBCDA) and etoposide as consolidation in patients with stage III and IV epithelial ovarian cancer. A total of 40 patients with stage III and IV ovarian cancer were entered into the study. Ifosfamide 1 glm² plus mesna 1 glm² was given as six hour infusion daily for six days and CDDP 75 mglm² was given on day seven. Patients completing six cycles of systemic therapy underwent second look laparotomy followed by four cycles of IP chemotherapy with CBCDA 300 mglm² and etoposide 200 mglm². Of the 40 patients entering the protocol 27 patients completed six cycles with a complete remission (CR) of 65% and overall response of 67.5%. Twenty-two patients underwent second look laparotomy with pathological CR in ten patients, microscopic disease in seven and macroscopic disease in five. Eleven patients completed four cycles of IP chemotherapy. At 52 months the overall survival (OS) was 36%. The disease free survival (DFS) at 45 months was 38%. Factors affecting OS were ascites (p<0.011), stage (p<0.04), weight change (p<0.017), residual disease (p<0.001), number of chemotherapy cycles (p<0.0001) and IP chemotherapy (p<0.006). Presently 35% patients are alive in CR, 15% are alive with disease, one patient has been lost to follow up while 47.5% have died. Of these four patients had progressive disease, seven relapsed, four died due to treatment related complications and two died in CR due to other causes. Subset analysis of 22 patients who had second look laparotomy and completed four cycles of IP chemotherapy revealed a distinct survival advantage. IFOS+CDDP is an effective combination as first time treatment in advanced ovarian cancer. IP chemotherapy is effective as consolidation and seems to provide a significant survival advantage. Further studies with larger number of patients need to be done to confirm these results.     

联合化疗方案治疗老年晚期胃癌的临床疗效和安全性分析

目的探讨临床常用晚期胃癌联合化疗方案治疗老年胃癌的临床疗效和安全性。方法回顾性研究2010年1月至2012年12月期间一线接受联合化疗的老年（年龄≥65岁）晚期胃癌患者20例。化疗2月后评价疗效,化疗期间监测药物毒性反应,对无进展生存时间（PFS）和总生存期（OS）进行随访。结果接受联合化疗的老年胃癌患者客观缓解率为15%,疾病控制率为90%,中位PFS和OS分别为6月和20.1月;分层分析显示仅肿瘤分期与患者PFS（P〈0.01）和OS（P〈0.01）显著相关,与年龄（≤75岁vs〉75岁）或化疗方案无关;化疗期间全部Ⅲ~Ⅳ度药物毒性反应的发生率为35%。结论采用联合化疗方案治疗晚期老年胃癌患者毒性反应在可耐受范围内,并可带来生存获益,方案和剂量的选择值得进一步临床研究。     

Pancreatic cancer: progress in cancer therapy

Pancreatic cancer continues to be a highly lethal disease. In fact the overall 5-year survival rate is less than 4% and has hardly improved over the past two decades. Surgery is the only potential curative treatment, but the majority of patients have an unresectable disease at the diagnosis. After the demonstration in 1997 that gemcitabine could lead to an improvement in clinical benefit and overall survival this chemotherapy agent became the standard of care for advanced pancreatic cancer patients. Several authors tried to improve results obtained with single agent gemcitabine by exploring the activity of novel chemotherapy on biologically targeted agents in combination with gemcitabine. Unfortunately, global findings were often disappointing with only a marginally significant survival benefit. New treatment strategies and a more careful evaluation of innovative therapies are clearly needed for this disease. In this review we will focus on treatment strategies both in resectable and advanced pancreatic cancer.     

Management of locally advanced and metastatic colon cancer in elderly patients

Colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years.Sixty percent are diagnosed over the age of 65 years and 36%are 75 years or older.At diagnosis,approximately 58% of patients will have locally advanced and metastatic disease,for which systemic chemotherapy has been shown to improve survival.Treatment of cancer in elderly patients is more challenging due to multiple factors,including disabling co-morbidities as well as a decline in organ function.Cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations.In locally advanced disease,fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts.A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease.When treating elderly patients with colon cancer,one has to consider drug pharmacokinetics and pharmacodynamics.Since chronological age is a poor marker of a patient’s functional status,several methods of functional assessment including performance status and activities of daily living(ADL)or instrumental ADL,or even a comprehensive geriatric assessment,may be used.There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual.Important considerations when treating elderly patients include convenience and tolerability.This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer.