Maintenance Chemotherapy of Stage Ⅲ Epithelial Ovarian Carcinoma-Focusing on Individualized Maintenance Chemotherapy

OBJECTIVE To investigate the role of maintenance chemotherapy on stage Ⅲ ovarian carcinoma. METHODS A retrospective analysis was conducted of 47 stage Ⅲ ovarian carcinoma patients with clinical complete remission after first-line chemotherapy. Among these patients, 21 cases were treated with maintenance chemotherapy, while the other 26 cases were free of treatment until progression. The 2 groups were compared with respect to progression-free survival （PFS） and overall survival（OS）. RESULTS The median PFS and OS were not significantly different between the 2 groups. For those patients, in a subgroup of suboptimal surgery （residual disease 〉2 cm）, the median PFS was 110 weeks and 56 weeks and the median OS was 223 weeks and 157 weeks for the maintenance and non-treated respectively. Both PFS and OS values favoured the maintenance group, P=0.004 and P=0.015 respectively. In a subgroup of optimal surgery （residual disease ≤2 cm）, the differences were not significant. CONCLUSION Patients with stage III ovarian carcinoma with clinical complete remission may benefit from maintenance chemotherapy, if the residual disease is 〉2 cm. To those with a residual disease ≤2 cm, the maintenance chemotherapy maybe of no value. So “individualized maintenance chemotherapy” should be conducted in the clinical setting.     

Chemotherapy drug resistance — a panel discussion

Considerable insight into the problem of drug resistance has emerged in the past few years. An understanding of why tumors develop drug resistance is now at hand both from theoretical points of view and from experimental and clinical data. Experimental models of drug resistance, particularly related to the surface P-glycoprotein, have been remarkably successful in teaching us why tumor cells in culture develop resistance to common therapeutic agents. In this panel discussion, the clinical relevance of these and other proposed mechanisms will be examined, with the hope of providing an up-to-date overview on this exciting field.A series of teleconferences has been organized under the auspices of Bristol-Myers to address several major current questions in oncology. A panel of recognized experts with a moderator has been assembled to discuss each question, and we are reporting a number of these discussions in Breast Cancer Research and Treatment. This is reprinted from Ocology Viewpoints, courtesy of Bristol-Myers Oncology Division, Evansville IN 47721, USA.     

Beyond Doublet Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Combination of Targeted Agents with First-Line Chemotherapy

The first-line treatment of advanced non–small-cell lung cancer (NSCLC) has evolved significantly over the past 5 years. As recently as 15 years ago, best supportive care (BSC) was considered an acceptable option for most patients with advanced or metastatic NSCLC, based on the concern that toxic effects of systemic chemotherapy overshadowed any potential benefits. The enhanced efficacy of platinum-based doublet chemotherapeutic regimens led to increases in overall patient survival relative to BSC. However, overall survival (OS) appeared to plateau, even with the introduction and refinement of these regimens. The addition of novel targeted agents targeting growth pathways to platinum-based regimens failed to overcome the 7.8- to 10.5-month survival barrier. After many phase III clinical trials, which involved tyrosine kinase inhibitors, matrix metalloproteinase inhibitors, protein kinase C inhibitors, and retinoids, this survival barrier had yet to be surmounted, although in some cases certain subgroups benefited, suggesting specific molecular correlations. Recently, inhibition of components of the angiogenesis pathway with the addition of bevacizumab to a platinum-based doublet led to statistically significant increases in OS, progression-free survival, and response rate relative to chemotherapy alone. This advance pushed the median survival of selected patients with advanced or metastatic NSCLC who met the eligibility criteria of the trial over the 12-month mark, thus offering patients and clinicians hope for more incremental advances in the future.     

Synergistic Antitumor Efficacy of Oncolytic Adenovirus Combined with Chemotherapy

Objective： Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods： We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results： In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion： We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.     

Catheter-related Complications in Postoperative Intraperitoneal Chemotherapy for Gastric Cancer

Objective： To analyze catheter-related complications during postoperative Intraperitoneal chemotherapy （IPCT） for gastric cancer. Methods： From December 2003 to April 2007, 80 patients with gastric cancer were treated with postoperative IPCT using central venous catheters （CVCs）, during which the complications that occurred in association with CVCs were documented and analyzed. Results： Catheter-related complications were seen in 10 out of the 80 patients, yielding a total complication rate of 12.5%. Main complications included abdominal pain （3.8%）, local infection （1.3%）, catheter obstruction （2.5%）, leakage （2.5%） and dislocation （2.5%）. All patients successfully finished their IPCT, the success rate was 100%. There occurred no severe complications or treatment-related deaths. Conclusion： It is convenient and safe to carry out postoperative IPCT for gastric cancer using CVCs, which, with a low catheter-related complication rate, should be recommended for more clinic use.     

Chemotherapy or Endocrine Therapy for Metastatic Breast Cancer?

Hispanic women differ from non-Hispanics in breast cancer incidence, stage at diagnosis, and survival. Ethnic differences in genetic makeup, reproductive patterns, diet, socioeconomic status, physical activity, and other unidentified cultural factors may be responsible for the disparity. This study investigated occurrences of p53 tumor suppressor gene mutations in South Florida white Hispanic and white non-Hispanic women with primary breast cancer. Tumor tissues were obtained from a consecutive series of women with breast cancer who underwent breast resection at the Jackson Memorial Hospital, Miami, Florida between 1984 and 1986. A total of 231 women with primary breast cancer, aged 31–85 years, were included in the study. Among them, 64 (27.7%) were white Hispanic and 167 (72.3%) were white non-Hispanic. The majority of the patients were white non-Hispanics (72.3%). Compared to white non-Hispanics, however, white Hispanics had significantly higher proportions of tumors larger than 2cm (53.1% v.s. 28.7%, p = 0.00) as well as larger tumor size at diagnosis (mean: 4.2 v.s. 3.0cm, p = 0.00). The p53 gene mutation rate was significantly lower in white Hispanics than in white non-Hispanics (51.6% v.s. 70.7%, p = 0.01). Furthermore, among node-negative breast cancer patients, after adjustment for tumor size at diagnosis, logistic regression results showed that white Hispanics were 71% less likely than white non-Hispanics to carry p53 mutations (OR = 0.29 and 95% CI = 0.09–0.91). We conclude that white Hispanic women with breast cancer might have lower p53 gene mutation prevalence than white non-Hispanic women.     

First-line Pembrolizumab Versus Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Non–small-cell Lung Cancer: A Systematic Review and Network Meta-analysis

BackgroundThis study aimed to comprehensively review the available evidence regarding the efficacy of first-line pembrolizumab for advanced/metastatic non–small-cell lung cancer (NSCLC), and to compare pembrolizumab monotherapy versus pembrolizumab plus chemotherapy versus chemotherapy alone.Materials and MethodsA search of the PubMed, EMBASE, and Cochrane Library databases was performed in July 2018, and abstracts from the American Society of Clinical Oncology meetings (2015-2018) were reviewed. Summaries of the results were pooled using a random-effect model to determine the pooled hazard ratio (HR) for progression-free survival (PFS), overall survival (OS), and their 95% confidence intervals (CIs). A network meta-analysis was used to indirectly compare pembrolizumab monotherapy with pembrolizumab plus chemotherapy.ResultsA total of 4 relevant phase III trials comprising 2754 patients were identified. Pembrolizumab (with or without chemotherapy) led to significant improvements in OS and PFS, irrespective of the programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS). In particular, for the subgroup with PD-L1 TPS ≥ 50%, the HR of PFS was 0.49 (95% CI, 0.32-0.76; P = .001), and that of OS was 0.57 (95% CI, 0.45-0.73; P < .001). In terms of PFS, pembrolizumab plus chemotherapy was superior to pembrolizumab monotherapy with an HR of PFS 0.52 (95% CI, 0.27-0.99; P = .048) for the subgroup with PD-L1 TPS ≥ 50%.ConclusionsFor patients with NSCLC with PD-L1 TPS ≥ 50%, pembrolizumab plus chemotherapy has a better PFS than pembrolizumab monotherapy in this meta-analysis. To confirm this finding, a prospective phase III trial that directly compares the treatments is warranted.     

Chemotherapy for advanced cholangiocarcinoma: what is standard treatment?

Cholangiocarcinoma is a relatively uncommon malignancy, that presents late in the vast majority of cases. Overall survival rates are extremely poor and treatment options remain limited in patients with inoperable, recurrent or metastatic disease. Systemic chemotherapy has historically had little impact on the natural history of this disease, owing to both the absence of agents with substantial activity and the overall morbidity of treatment in this patient population. Response rates with 5-fluorouracil have been 10% at best, with a median survival of 6 months. However, there has been interest in the use of newer cytotoxic drugs and combination regimens in advanced cholangiocarcinoma, and Phase II trials have reported much improved results. This review examines this data and assesses whether a new standard of care for advanced cholangiocarcinoma can be found.     

Platinum-Based Chemotherapy ‘Rechallenge’ in Advanced Non-ovarian Solid Malignancies

Platinum-based chemotherapy forms the backbone of treatment for many solid cancers. However, resistance inevitably develops in those with advanced disease. Platinum rechallenge is a well-established concept in the management of ovarian cancer, small cell lung cancer and germ cell tumours. In other solid malignancies there is a lack of quality evidence to support platinum rechallenge, yet it is a widely adopted strategy. Often, patients are within the last year of life, making questions of efficacy, treatment-related toxicity and quality of life critical factors for treatment recommendations. In this overview we appraise the available evidence for platinum rechallenge and strategies being developed to attempt resensitisation of tumours to platinum-based chemotherapy.     

What is the Role of Chemotherapy in Endometrial Cancer?

Adjuvant pelvic radiotherapy has the potential to eradicate micrometastases within the irradiated field but has not resulted in survival improvements in randomized studies. This illustrates the need for systemic therapy. Chemotherapy, mainly with anthracyclines, platinum compounds, and taxanes, renders high response rates although this unfortunately translates in only modest improvements in progression-free and overall survival. Better systemic treatments need to be developed. Investigations of the molecular mechanisms of endometrial cancer have identified possible targets for therapy. In advanced endometrial cancer one study shows that chemotherapy is better than whole abdominal radiotherapy, while in the adjuvant situation the combination of chemotherapy and radiotherapy appears promising.