Transient Carcinoembryonic Antigen Elevations During Adjuvant Chemotherapy for Colorectal Cancer Reflect the Burden of Residual Micrometastatic Disease

BackgroundCarcinoembryonic antigen (CEA) testing is routinely used to monitor the progress of patients with advanced cancer on treatment, or else to detect relapse during follow-up, particularly in colorectal cancer (CRC). Although CEA levels have been reported to rise during adjuvant drug therapies, the mechanism of such ‘surges’ is not clear. This study was conducted to clarify the clinical significance of this phenomenon.Patients and MethodsWe conducted a retrospective analysis of CEA levels in 88 consecutive patients receiving adjuvant chemotherapy in our center: 39 patients with primary CRC and a comparison cohort of 49 patients with breast cancer treated with adjuvant chemotherapy. In the event of 2 serial CEA increases, endoscopic and/or imaging investigations were performed to exclude recurrence. Subset analyses were based on nodal status and primary tumor type.ResultsPrimary resection was associated with significant CEA decline in patients with CRC but not in those with breast cancer. Forty-three patients (48.9%) experienced CEA fluctuations exceeding 0.5 ng/mL during adjuvant chemotherapy; CEA increases indicated true recurrence in 2 patients (4.7%). Adjuvant CEA surges occurred both more often and more extensively in disease associated with ≥ 4 positive nodes in patients with CRC but not in patients with breast cancer (P < .05).ConclusionBoth the frequency and extent of CEA surges during adjuvant chemotherapy parallel the severity of preoperative nodal involvement in CRC but not in breast cancer, suggesting that such surges reflect tumorilytic effects on occult disease in patients with CRC only. However, whether these CEA surges predict survival that is inferior (ie, because of greater burden of residual disease) or superior (ie, because of greater tumorilytic efficacy) to that of stage-matched ‘nonsurge’ patients, remains to be determined by larger, prospective CRC studies.     

Biological Characteristics of Micrometastatic Cancer Cells in Bone Marrow

There is emerging evidence that epithelial tumor cells are able to disseminate to secondary organs at an early stage of primary tumor development. One of the most prominent secondary organs screened for this type of dissemination is bone marrow. Even in cancer entities where overt skeletal metastases are rare (e.g., colorectal and ovarian cancer), bone marrow is a prognostically relevant indicator organ for the presence of hematogenous micrometastases. The currently available data suggest that bone marrow micrometastases represent a selected population of dormant cancer cells which still express a considerable degree of heterogeneity. The analysis of micrometastatic cells will open a new avenue to assess the molecular determinants of early tumor cell dissemination and subsequent outgrowth into overt metastases. Moreover, monitoring the elimination of bone marrow micrometastases and identification of treatment-resistant tumor cell clones may help to increase the efficacy of adjuvant therapy. This review summarizes the current knowledge on the biological characteristics of micrometastatic cancer cells in bone marrow of patients with solid epithelial malignancies.     

化疗在肺癌综合治疗中的作用

随着有效新药的发展,防治化疗不良反应等辅助治疗的进步,化学药物治疗晚期非小细胞肺癌,特别是小细胞肺癌疗效明显提高,因而,在肺癌的综合治疗中有不可取代的功能。其应用：治疗局部晚期或有播散性病变及复发患者;新辅助化疗;辅助化疗;化学预防。结合临床实践与文献重点讲座其治疗原则与新方法。     

Role of Non-Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer

Platinum-based chemotherapy regimens have been the mainstay of systemic chemotherapy in advanced NSCLC. However, substantial toxicity impairs the survival and symptom control advantages of cisplatin- and even carboplatin-containing regimens. With the advent of newer active agents in the 1990s, investigators began conducting clinical studies with the aim of potentially eliminating platinum from initial therapy for patients with advanced NSCLC. Conceptually, three major hypotheses were tested in phase III trials: (i) single, non-platinum agents are equal in efficacy to platinum in combination with these agents; (ii) non-platinum combinations are potentially more effective than platinum-based therapy; and (iii) non-platinum combinations are at least equally efficacious, but less toxic than, platinum-based therapy. An overall analysis of phase III data indicates that combinations of these newer agents with platinum are superior to the single agent alone and that combinations of non-platinum agents are no more effective than platinum-based therapy. Non-platinum therapy has a different and perhaps marginally improved toxicity spectrum compared with platinum-based therapy. In the few studies utilizing a formal quality-of-life analysis, no differences have been detected. Therefore, while several non-platinum regimens have been validated in phase III trials as reasonable alternatives to platinum-based therapy, they have not been proven to be clearly superior.     

Role of Chemotherapy in Peritoneal Carcinomatosis in Metastatic Colorectal Cancer

Peritoneal carcinomatosis from colorectal cancer is increasingly recognized as a special form of metastatic disease. This review focuses on the efficacy of systemic chemotherapy in the setting of peritoneal carcinomatosis. Peritoneal carcinomatosis-affected individuals succumb to their disease earlier than those without known carcinomatosis, with an approximately 30 % reduction in overall survival. Modern cytotoxic combination chemotherapy incorporating oxaliplatin and irinotecan has resulted in marked improvement of overall survival among carcinomatosis patients, but not to the same extent as for non-carcinomatosis patients. Biologicals are also associated with increased overall survival, but still seem to underperform in the carcinomatosis patient. Efficacy of 5FU monotherapy seems negligible. Evidence suggests future trials should be stratified by peritoneal carcinomatosis status. Complementary benefits of systemic chemotherapy and cytoreductive surgical approaches warrant further studies.     

Role of Non-Taxane-Containing Chemotherapy in Advanced Non-Small Cell Lung Cancer

Treatment for advanced-stage NSCLC generally includes the use of systemic chemotherapy as well as biologic therapies (targeted therapy) at later stages of the disease. However, in general, NSCLC is moderately sensitive to the currently available cytotoxic drugs, so the intention of chemotherapeutic treatment in the advanced setting is mainly palliative. Several treatment regimens are available, but in the first-line setting, treatment traditions differ both within countries and between various parts of the world. The role of taxane-platinum chemotherapeutic combinations (mainly used in North America) has been questioned in the palliative setting since these combinations are known to cause neutropenia, skin and nail problems, as well as neurological toxicity. This review aims to summarize the current knowledge about the role of non-taxane therapy for patients with advanced NSCLC, with a focus on gemcitabine, vinorelbine, etoposide, pemetrexed, irinotecan, epidermal growth factor receptor (EGFR)-inhibiting agents, angiogenesis inhibitors, and small molecules. The compilation of literature in the present review indicates that the use of non-taxane treatment for patients with advanced NSCLC has an anti-tumor effect that is not different from that which can be seen with various taxane combinations. Furthermore, the combination of cisplatin with gemcitabine or vinorelbine seems to be a most compelling regimen in the first-line setting because of its modest toxicity (when administered by experienced staff), favorable clinical response, and relatively low drug cost. It is also clear that the novel therapies (EGFR inhibitors and inhibitors of angiogenesis) that have been approved so far will be of great clinical value; however, their use will be restricted to small, well defined, subpopulations of patients. The great challenge now is to define the populations benefiting from these novel therapies.     

单药吉西他滨治疗复发性乳腺癌的体外实验研究

目的探讨吉西他滨用于复发性乳腺癌患者的治疗效果和应用前景。方法对原发性和复发性乳腺癌患者的癌组织标本,采用胶原酶消化法获取乳腺癌原代细胞,应用原代培养和MTT法检测5种化疗药物在体外对乳腺癌原代细胞的杀伤力。结果对原发性乳腺癌患者,紫杉醇和多西他赛的杀伤效果(敏感率分别为91.04%,92.54%)优于阿霉素、表阿霉素和吉西他滨(敏感率分别为73.13%,74.63%,77.61%)(P<0.01);对复发性乳腺癌原代细胞,吉西他滨的杀伤效果(敏感率为77.78%)则明显优于阿霉素、表阿霉素和紫杉醇、多西他赛(敏感率分别为37.04%,40.74%,66.67%,66.67%)(P<0.01)。结论吉西他滨可以作为复发性乳腺癌患者化疗的一线药物。     

Role of Neoadjuvant Chemotherapy in the Management of Advanced Ovarian Cancer

Objective: To analyze efficacy of neoadjuvant chemotherapy for advanced ovarian cancer. Materials andMethods: A total of 107 patients with advanced ovarian cancer undergoing cytoreductive surgery were dividedinto a neoadjuvant chemotherapy group (n=61) and a primary debulking group (n=46) and retrospectivelyanalyzed. Platinum-based adjuvant chemotherapy was applied to both groups after cytoreductive surgery andeoverall and progression-free survival times were calculated. Results: No significant difference was observed induration of hospitalization (20.8±6.1 vs. 20.2±5.4 days, p>0.05). The operation time of neoadjuvant chemotherapygroup was shorter than the initial surgery group (3.1±0.7 vs. 3.4±0.8 h, p<0.05). There were no significantdifferences in median overall survival time between neoadjuvant chemotherapy group and surgery group (42 vs.55 months, p>0.05). Similarly, there was no difference in median progression-free survival between neoadjuvantchemotherapy group and surgery group (16 vs. 17 months, p>0.05). The surgical residual tumor size demonstratedno significant difference between initial surgery and neoadjuvant chemotherapy groups (p>0.05). Multivariateanalysis showed that more than 3 cycles of regimen with neoadjuvant chemotherapy was associated with moreresistance to chemotherapy compared with patients without receiving neoadjuvant chemotherapy (OR: 5.962,95%CI: 1.184-30.030, p<0.05). Conclusions:Neoadjuvant chemotherapy can shorten the operation time. However,it does not improve survival rates of advanced ovarian cancer patients.     

辅助化疗在早期可手术非小细胞肺癌治疗中的地位

肺癌患者术后复发转移是临床治疗失败的主要原因,因此亟待一种更系统的治疗手段来完善患者的治疗计划,以降低复发率、延长生存期。辅助化疗(包括新辅助化疗、术后辅助化疗、靶向药物辅助化疗)应运而生。本文就辅助治疗领域的研究进展进行综述。     

进展期胃癌术前介入化疗的疗效观察

[目的]观察进展期胃癌术前介入化疗的临床疗效和病理变化。[方法]对65例进展期胃癌患者进行术前动脉介入化疗,采用Seldinger技术,根据癌灶部位选择性动脉插管,方案为:5鄄Fu750mg/m2,MMC10mg/m2,DDP60mg/m2。化疗后7~10天手术,对术后胃标本进行组织病理学检查,同时观察术后生存率。[结果]65例均获手术切除,组织病理学改变总有效率70%,术后1年和2年生存率分别为96.92%和89.23%。[结论]术前介入化疗有助于提高手术切除率和术后生存率,且并发症较少,可作为进展期胃癌的术前常规辅助化疗方法。     

The Role of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer

Overall outcomes for women with epithelial ovarian cancer (EOC) remain relatively poor, and superior methods of treatment are needed. EOC is a peritoneal surface malignancy that is relatively sensitive to chemotherapy agents, making it a good target for i.p. chemotherapy. Because there is strong laboratory data demonstrating the ability of hyperthermia to increase the efficacy of chemotherapeutic agents, the addition of hyperthermia to i.p. chemotherapy, hyperthermic intraperitoneal chemotherapy (HIPEC), makes theoretical sense. This article reviews the current literature and discusses the possible role for HIPEC in EOC at significant natural history time points: front line, at the time of interval debulking, in consolidation, and for recurrent disease. The conclusion is that much further research is needed but that HIPEC could sensibly be researched at all the natural history time points in EOC.     

介入化疗在中晚期宫颈癌治疗中的作用

[目的]探讨介入化疗在中晚期宫颈癌治疗中的作用。[方法]81例Ⅱb～Ⅲb期宫颈癌患者采用顺铂(DDP)为主的介入化疗同时进行传统的放射治疗(综合治疗组),其中14例患者治疗后行根治性手术切除。同期84例宫颈癌患者仅作单纯放射治疗(对照组)。[结果]综合组有效率93.83%,单放组78.57%,两组比较有显著性差异(P<0.05)。远期随访:Ⅱ期的5年生存率两组分别为75.0%和65.0%、Ⅲ期50.0%和40.3%。综合组疗效虽然比单放组好,但统计学处理两组差异无显著性(P>0.05)。[结论]介入治疗配合放疗提高中晚期宫颈癌的近期疗效,但对远期疗效没有改善。     

Long-Term Complete Remission of Oral Cancer after Anti-Neoplastic Chemotherapy as Single Treatment Modality: Role of Local Chemotherapy

Abstract

The impact of intra-arterial local chemotherapy on squamous cell carcinomas of the oral cavity is doubtful when considering long-term survival, especially in cases of nodal involvement. But even in patients with strictly local disease it is not possible to determine the effect of intra-arterial chemotherapy because it is mainly used as a neoadjuvant treatment modality. In the present paper, long-term courses of two patients are described who refused any further treatment after one cycle of intra-arterial chemotherapy with cisplatin followed by systemic chemotherapy with 5-fluorouracil and one cycle of intra-arterial chemotherapy with high-dose cisplatin, respectively. The aim of the paper is to demonstrate the potential of local chemotherapy in responders. The impact of this treatment modality in incurable patients is discussed, too. This may offer a point in favor of use of intra-arterial chemotherapy in combination treatment regimens.     

Chemotherapy of Gastric Cancer

Despite a steady decline in incidence over the past five decades in this country, gastric carcinoma continues to represent a major health problem. From the turn of the century through the 1930s, gastric cancer was the leading cause of death in the United States (1). Despite the subsequent decline, the American Cancer Society estimated that approximately 25,000 new diagnoses of gastric cancer would be made in 1988, and that deaths due to this malignancy would exceed 14,400 in the same year. At present, it is the eighth most common cause of cancer death in this country.