Pseudomyxoma peritonei treated with complete resection and immediate intraperitoneal chemotherapy

AIM: Pseudomyxoma peritonei remains a fatal disease. This clinical pathological entity based on the presence of mucin includes different prognostic groups. Complete resection of macroscopic lesions, combined with immediate intraperitoneal chemotherapy to treat remnant infra-millimetric disease, might improve survival. The aim of this prospective study was to evaluate this treatment strategy. METHODS: Thirty-six patients with pseudomyxoma peritonei underwent resection of supra-millimetric lesions then were given either early postoperative intraperitoneal chemotherapy (5 days) (before January 1996) or intraoperative chemohyperthermia treatment (after January 1996). During this same period, only partial resection of the macroscopic lesion was possible in 15 patients; these patients were not given peritoneal chemotherapy. RESULTS: Postoperative mortality was 13.8% (n=5), including 2 deaths not specifically due to the procedure. Morbidity, including severe and non-severe complications was 44%. After a mean follow-up of 48 months, the overall 5-years survival rate was 66%, and disease-free survival rate was 55% (including the postoperative deaths). The main prognostic factor in this series was the pathological grading: 5-years survival was 74% for grade 1 tumors versus 54% for grades 2-3 (P=0.05). CONCLUSION: The main prognostic factor of the pseudomyxoma peritonei, after the completeness of the resection, is the pathological grading. The addition of an intraperitoneal chemohyperthermia improves long-term survival of grades 2-3 tumors and perhaps that of grade 1 (agreement of experts). This treatment is more easily performed, more well-tolerated, and more efficient when performed early.     

Angiocentric immunoproliferative lesions: a clinicopathologic spectrum of post-thymic T-cell proliferations

Twenty-three patients with angiocentric immunoproliferative lesions (AILs) including angiocentric lymphoma were evaluated clinically and pathologically. Pathologic subclassification performed without knowledge of the clinical outcome divided the cases into three histologic grades on the basis of cellular atypia and degree of inflammatory background. Immunophenotypic studies of lesions from six patients demonstrated a mature T-cell phenotype with a predominance of CD4-positive cells. Abnormalities of antigenic phenotype were demonstrated in only one case, classified as grade III. That tumor also demonstrated a clonal rearrangement of the T beta gene. Progression to malignant lymphoma following initial immunosuppressive therapy with cyclophosphamide and prednisone occurred in three of nine patients with grade I lesions and four of six patients with grade II lesions. The supervening lymphomas were usually refractory to subsequent aggressive chemotherapy, with only one patient achieving a complete remission. In contrast, seven of eight patients with grade III lesions achieved a complete remission with aggressive combination chemotherapy, two of whom also received supplemental radiation therapy. These studies support the concept that the AILs represent a spectrum of post-thymic T-cell proliferations. The single most important prognostic indicator for ultimate survival is achievement of an initial complete remission. Patients treated initially with conservative chemotherapy may be compromised in their ability to achieve a complete remission if they progress to a higher grade lesion.     

Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407)

Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.     

Efficacy and safety of pemetrexed maintenance chemotherapy for advanced non-small cell lung cancer in a real-world setting

BackgroundPemetrexed maintenance therapy offers a survival benefit in patients with nonprogressive advanced nonsquamous non-small cell lung cancer (NSCLC) with good tolerability. This study was designed to analyze the efficacy and safety of pemetrexed maintenance chemotherapy in advanced nonsquamous NSCLC patients in a real-world setting.MethodsThe response rate (RR) and adverse events in 71 nonsquamous NSCLC patients treated with pemetrexed-based chemotherapy were observed until disease progression or unacceptable toxicities. Measures of survival were analyzed during follow-up.ResultsOf 69 efficacy-evaluable patients, the objective response rate (ORR) was 46.4% and the disease control rate (DCR) was 98.6%. ORR showed no significant difference between patients who received pemetrexed as first-line therapy and those who received pemetrexed as second-line or higher treatment. The median treatment cycle for all patients was 8. The median progression-free survival (PFS) was 9.5 months (m) and median overall survival (OS) was 30.5 m. The univariate and multivariate analyses showed that the number of chemotherapy cycles was an independent factor for PFS. The most common adverse reactions were grade 1 to 2 hematologic toxicities, gastrointestinal reactions, and liver enzyme abnormalities. Only 1 patient experienced a grade 3 gastrointestinal event.ConclusionsPemetrexed maintenance chemotherapy can improve PFS in patients with advanced nonsquamous NSCLC with good tolerability.     

Advanced gastric cancer:Current treatment landscape and future perspectives

Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease(locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2(HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer.     

Primary colorectal lymphoma

PURPOSE: The purpose of this study was to review the clinical presentation and characteristics of primary colorectal lymphoma, analyze the prognostic factors, and assess the results of treatment with adjuvant chemotherapy. METHODS: We identified 37 cases at our institution between 1980 and 1996. They comprised 0.48 percent of all cases of colon malignancies (37/7,658) during this period. The following clinical information was obtained: age, gender, signs and symptoms, tumor site, tumor size, histology grade, pathology, and adjuvant chemotherapy. RESULTS: The most common presenting signs and symptoms were abdominal pain (62 percent), abdominal mass (54 percent), and weight loss (43 percent). The most frequent site of involvement was the cecum (45 percent). Histologically, 29 (78 percent) were classified as high-grade, and 8 (22 percent) as intermediate-grade-to-low-grade lymphoma. Nine (24.3 percent) of the cases were Stage EI, 23 (62.2 percent) were Stage EII, and 5 (13.5 percent) were Stage EIV. Twenty-one (57 percent) cases received adjuvant chemotherapy. The five-year survival rate was 33 percent for all patients and 39 percent for patients treated with combination chemotherapy. Overall median survival time was 24 months and 36 months for those with adjuvant chemotherapy. Only histology grade, among the factors examined, was a significant prognostic factor for survival. The mean survival time of the patients with Stage II disease who received chemotherapy was 117.4 months, and it was 47.9 months for the patients with Stage II disease who did not received chemotherapy. CONCLUSIONS: In our retrospective study high-grade lymphoma was the only significant adverse prognostic factor for survival. Receiving adjuvant chemotherapy significantly improved survival in patients with Stage II disease. Patients with diffuse large-cell type had better survival than patients with small noncleaved-cell type in Stage II high-grade lymphoma.     

Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer

BACKGROUND: The aim of this phase II study was to determine the efficacy of gemcitabine plus cisplatin chemotherapy in patients with advanced biliary tract cancer. METHODS: Eligibility criteria included histologically confirmed adenocarcinoma with measurable tumor in the biliary tract that was unresectable and either locally advanced or metastatic. Patients received a combination of gemcitabine (1000 mg/m(2) intravenously [IV] on days 1, 8, and 15) and cisplatin (75 mg/m(2) IV on day 1). Cycles were repeated every 28 days. Objective tumor response rates and toxicities were evaluated according to World Health Organization criteria. RESULTS: Twenty-seven patients were enrolled in the study and a total of 120 cycles of chemotherapy were administrated. Objective partial response was observed in nine (33.3%) patients, while stable disease was found in seven (25.9%) patients. The median survival time was 10.0 months and the 1-year survival rate was 36%. Median time to disease progression was 5.6 months. The most common grade 3-4 toxicities were leukopenia (25.9%), anemia (29.6%), thrombocytopenia (22.2%), and vomiting (18.5%). Only one patient was hospitalized for chemotherapy-related complications. CONCLUSION: Gemcitabine and cisplatin combination chemotherapy is an effective, safe, and well-tolerated regimen for the treatment of advanced biliary tract cancer.     

Major prognostic factors in patients with T- and B-cell lymphomas

Major prognostic factors were analyzed by Cox proportional hazard model in 311 patients with B-lymphoma and 141 with T-lymphoma, who were treated with combination chemotherapy as the initial therapy during 1975 to 1987. Poor prognosis was associated with high grade pathology, increasing number of extranodal lesions, advanced stage, initial combination chemotherapy without doxorubicin, low total protein and intestinal lesion in B-lymphoma, but with increasing number of involved lesions, high LDH, low total protein, anemia, skin lesion and patients treated before 1982 in T-lymphoma. First three factors of each disease were the most important with risk ratio more than 2.5. New risk group was made from combination of the factors, which was ordered from low to high hazard rate. The new risk groups for T- and B-lymphoma are usefull for estimation of prognosis and determination of adequate chemotherapy of the patients. The prognostic factors of T-lymphoma were completely different from those of B-lymphoma, suggesting that T- and B-lymphoma are different disease and should be analyzed separately.     

Combination chemotherapy in patients with malignant pleural effusions from non-small cell lung cancer : cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support

OBJECTIVES: Malignant pleural effusions develop frequently in patients with non-small cell lung cancer (NSCLC), and the prognosis for these patients is very poor. We evaluated the role of systemic chemotherapy for patients with malignant pleural effusions from NSCLC. METHODS: We analyzed 34 patients who were found to have malignant pleural effusions in the course of diagnosis of 118 patients enrolled in three consecutive clinical trials on advanced NSCLC assessing combination chemotherapy of cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support. The objective response in the malignant pleural effusion was evaluated by CT scans every course with the response criteria of the Japan Lung Cancer Society. RESULTS: All patients had adenocarcinoma. The pleural effusion showed a complete response in 13 patients, a partial response in 7 patients, and no response in 14 patients. In the assessment of the efficacy of the treatment for the measurable primary or metastatic lesions, there was a partial response in 25 patients, no change in 8 patients, and progressive disease in 1 patient. The response rate in pleural effusions was 58.8%, and overall response in mensurable lesions was 73.5%. The median time to response and duration of response for pleural effusions were 54 days and 151 days, respectively. The median survival time and 1-year survival rates were 362 days and 48.5%, respectively. CONCLUSIONS: Both the response rate and survival data in this retrospective study suggest a high degree of activity of this combination chemotherapy in patients with malignant pleural effusions from NSCLC.     

Therapeutic implications of mediastinal involvement in advanced Hodgkin's disease

47 patients with advanced Hodgkin's disease (stage IIIB or IV) and mediastinal involvement, treated during the period 1969-78 and followed till death or from 36 to 126 months after initiation of therapy, were analysed. All 47 patients had received combination chemotherapy (MOPP or equivalent regimens). 20 had also received additional radiotherapy to mediastinum (and in some cases to other involved areas as well). The 2 treatment groups did not differ significantly with regard to the more important prognostic factors. Both in the case of stages IV and IIIB patients in the group treated with combination chemotherapy alone, remissions were significantly more often only partial, the frequency of relapse and of treatment failure was significantly higher, and relapse-free survival was significantly poorer than in the group treated with additional radiotherapy. Furthermore, survival from Hodgkin's disease and crude survival including all causes of death were significantly better for patients treated with combination chemotherapy plus mediastinal irradiation. Consequently, for patients with advanced Hodgkin's disease and mediastinal involvement a combined approach including radiotherapy as well as combination chemotherapy would seem advisable.     

Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer: A meta-analysis

AIM: To investigate the efficacy and safety of gemcitabine (Gem)-based combination chemotherapies for the treatment of advanced biliary tract cancer.METHODS: Clinical trials were identified by searching scientific literature databases (PubMed, EMBASE and the Cochrane Library) for studies published between 1975 and 2013. Two reviewers independently evaluated the relevant studies and manually searched references from these reports to locate additional eligible studies. The disease response and control rates, progression-free and overall survivals, and the grade 3-4 toxicities were evaluated by a meta-analysis. Odds-ratios (ORs) of the disease response and control rates and grade 3-4 toxicities, and the mean difference (MD) of both progression-free and overall survivals were calculated and used for statistical analysis.RESULTS: Seven randomized trials with a total of 858 patients were selected and included in the final analysis. The studies were divided into subgroups based on the chemotherapy regimens, including Gem-based and non-Gem-based chemotherapies. The overall analyses revealed that the patients treated with Gem-based combination chemotherapy had significantly higher disease response rates [OR = 1.69, 95% confidence interval (CI): 1.17-2.43; P = 0.01], a longer progression-free survival (MD = 1.95, 95%CI: 0.90-3.00; P = 0.00) and a longer overall survival (MD = 1.85, 95%CI: 0.26-3.44; P = 0.02). A higher incidence of grade 3-4 hematological toxicities, including leukopenia (OR = 2.98, 95%CI: 1.44-6.20; P = 0.00), anemia (OR = 2.96, 95%CI: 1.79-4.92; P = 0.00) and neutropenia (OR = 2.80, 95%CI: 1.39-5.64; P = 0.00) was found in the Gem-based combination chemotherapy group compared with the Gem monotherapy and non-Gem-based chemotherapy groups.CONCLUSION: Gem-based combination chemotherapy is a potential first-line treatment for advanced biliary tract cancer as a result of improved survival, though with additional toxicity.     

Pretreatment predictor of response,time to progression,and survival to intraarterial 5-fluorouracil/interferon combination therapy in patients with advanced hepatocellular carcinoma

Background Several studies have reported survival benefits of combination therapy with intraarterial 5-fluorouracil (5-FU) and subcutaneous interferon (IFN) α for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We investigated the pretreatment predictive factors of early response, time to progression (TTP), and survival in response to intraarterial 5-FU/IFN combination therapy. Methods Patients with nonresectable HCC and variable PVTT grades (without PVTT to PVTT in the trunk) received intraarterial 5-FU/IFN combination therapy (n = 55). Results After two courses of the combination therapy, 1 (2%), 15 (27%), 16 (29%), 12 (22%), and 11 (20%) of 55 patients showed complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or had dropped out (DO), respectively, when their early response to treatment was assessed. Univariate analysis identified only hepatitis C virus (HCV) antibody positivity as having significantly influenced the early response (P = 0.028) and TTP (P = 0.021). Multivariate analysis identified performance status (P = 0.003) and HCV antibody positivity (P = 0.007) as significant and independent determinants of survival. PVTT grade did not influence early response, TTP, or survival. The survival rate was significantly higher in patients who achieved CR or PR than in those that assessed as SD or PD, or DO (P < 0.0001, each). Conclusions HCV antibody positivity may be a significant pretreatment predictor of early response, TTP, and survival of patients with advanced HCC treated with 5-FU/IFN. CR or PR as the early response to the combination therapy might indicate a more favorable prognosis in patients with advanced HCC. PVTT grade did not seem to influence the efficacy of combination therapy.     

Toxicity and efficacy of chemotherapy for non-small cell lung cancer with cavitary lesions

BackgroundConcurrent chemoradiation in stage III non-small cell lung cancer (NSCLC) patients with cavitary lesions is reported to cause serious lung complications and is a predictor of poor survival. However, the efficacy and toxicity associated with chemotherapy for advanced NSCLC patients with cavitary lesions is not clear. We investigated the toxicities, particularly hemoptysis and cavity infection, and efficacy associated with chemotherapy for NSCLC patients with cavitary lesions.MethodsWe retrospectively reviewed consecutive patients who received first-line chemotherapy, including platinum-based chemotherapy, single-agent chemotherapy, or epidermal growth factor receptor-tyrosine kinase inhibitors, at our institution between January 2008 and December 2010.ResultsWe found tumor cavitation prior to treatment in 23 of 415 NSCLC patients (5.5%). The response rate of all the patients was 30%, and the median survival time (MST) was 8.9 months. The MST of the 15 patients treated with platinum-based chemotherapy was 11 months. Grade 1 bronchopulmonary hemorrhage occurred in 2 patients. Grade 3 cavitary infection occurred in 2 patients, resulting in the discontinuation of chemotherapy.ConclusionsThis study indicates that the toxicity of chemotherapy for NSCLC patients with cavitary lesions is tolerable; however, the development of cavitary infection should be carefully considered. In addition, this study suggests that the efficacy of chemotherapy for NSCLC patients with cavitary lesions is similar to the response rates reported in the literature; however, the survival of these patients may be worse than that for general NSCLC patients.     

Oral regimen consisting of UFT/UZEL for elderly patients with colorectal cancer

BACKGROUND/AIMS: A clinical trial has been planned to assess the safety and efficacy of oral administration of UFT and leucovorin (UZEL) in elderly patients with advanced colorectal cancer (CRC). METHODOLOGY: Twenty-six patients with advanced CRC who were over 70 years and considered ineligible for combination chemotherapy received oral UFT 300 mg/day and UZEL 75mg/day were administered orally for 28 days followed by a 7-day rest period. Treatment was repeated every 5 weeks until disease progression. RESULTS: A total of 106 cycles of UFT/UZEL were administered (median, four cycles; range, one to twelve cycles). UFT/UZEL was well tolerated. The response rate was 11% (3 partial responses, 16 stable diseases, and 7 progressive diseases). The median progression-free survival rate was 3.9 months and the median survival time was 9.8 months. Treatment-related grade 3 and 4 adverse events were not observed. CONCLUSIONS: Oral regimen consisting of UFT/ UZEL is effective and well tolerated in elderly patients with advanced CRC who are considered ineligible for combination 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.     

Importance of performance status for treatment outcome in advanced pancreatic cancer

Despite progress in the treatment of advanced and metastatic pancreatic cancer (PC), the outcome of this disease remains dismal for the majority of patients.Given the moderate efficacy of treatment, prognostic factors may help to guide treatment decisions. Several trials identified baseline performance status as an important prognostic factor for survival. Unfit patients with a Karnofsky performance status (KPS) below 70% only have a marginal benefit from chemotherapy with gemcitabine (Gem) and may often benefit more from optimal supportive care. Once, however, the decision is taken to apply chemotherapy, KPS may be used to select either mono- or combination chemotherapy. Patients with a good performance status (KPS = 90%-100%) may have a significant and clinically relevant survival benefit from combination chemotherapy. By contrast, patients with a poor performance status (KPS ≤ 80%) have no advantage from intensified therapy and should rather receive single-agent treatment.     

The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer

BACKGROUND/AIMS: Recently we have shown that NSC-631570 (Ukrain) is a safe and effective drug in the treatment of unresectable pancreatic cancer. The aim of this study was to determine the effectiveness of the combined treatment with Gemcitabine and NSC-631570 in the adjuvant treatment of resected advanced pancreatic cancer. METHODOLOGY: 30 patients received adjuvant chemotherapy following surgical resection for pancreatic cancer. Chemotherapy consisted of Gemcitabine according to the Burris-protocol with weekly infusions of 1000 mg/sqm. Immediately following Gemcitabine infusion 20mg of NSC-631570 were administered intravenously over 15 minutes. RESULTS: WHO grade II toxicities were observed in 53%, no WHO grade III or IV toxicities occurred. In 80% of the patients recurrence of the disease was observed. The relapse-free survival time was 21.7 months. The actuarial survival rates were 86.7% after one year, 76.6% after two years, 46.7% after three years and 23.3% after five years. The median survival time according to Kaplan-Meier regression analysis was 33.8 months. CONCLUSIONS: Adjuvant chemotherapy in advanced stages of pancreatic cancer using the combination of Gemcitabine and NSC-631570 is a safe treatment and seems to lead to a prolonged survival. Although further investigation is needed to confirm these results, the combined treatment of Gemcitabine and NSC-631570 is a promising therapy for the adjuvant treatment of resectable advanced pancreatic cancer.     

DIFFUSE HISTIOCYTIC LYMPHOMA: THE 20-YEAR EXPERIENCE OF AN AUSTRALIAN TEACHING HOSPITAL

There is a paucity of information regarding the natural history and treatment outcome of diffuse histiocytic lymphoma (DHL) in Australia. Case records from 80 patients treated for DHL at the Royal Adelaide Hospital between 1965 and 1985 were reviewed to determine treatment outcome and prognostic information. Pathological review of biopsy specimens confirmed the correct diagnosis in 78 patients. The Ann Arbor staging criteria were unsatisfactory for prognostic purposes. We identified three prognostic groups: Localised disease (82% five-year survival), Advanced disease marrow negative (36% five-year survival), and Advanced disease marrow positive (11 % five-year survival). An elevated plasma lactate dehydrogenase (LDH) and calcium (Ca⁺⁺) predicted a poorer outcome; no patient with a LDH > 500 IU achieved longterm survival (p < 0.001). Survival was identical for patients reclassified histologically as intermediate grade or high grade (Working Formulation). Localised disease was associated with a good prognosis (82% five-year survival) regardless of treatment modality. The outcome of patients with advanced disease has markedly improved over the last two decades, particularly with the introduction of combination chemotherapy containing doxorubicin in 1974 (p < 0.005). Using these regimens, complete remission was achieved in 65% of patients, with a 39% five-year survival.     

Phase II study of pirarubicin combined with cisplatin in recurrent ovarian cancer

Although 50%–80% of patients with advanced ovarian cancer demonstrate an objective response after platinum-based chemotherapy, a majority of these patients will ultimately experience a relapse of their disease. Effective second-line treatment for these patients is of the utmost importance. We performed a phase II study with cisplatin and pirarubicin (each drug 50 mg/m² i.v. every 28 days) in 17 patients with relapsed or persistent ovarian carcinoma. All patients had received platinum-containing primary chemotherapy. Overall survival from the time of diagnosis was 38.3 months (45.3 months in relapsed ovarian carcinoma and 28.3 months in ovarian carcinoma persisting after primary chemotherapy). Survival from entrance into the study was 13.0 months (14.2 months in relapsed disease and 11.2 months in refractory disease). Time to progression was 10.3 months. An objective response was observed in 4 patients and another 3 patients had stable disease. Major toxicity consisted of emesis (grade III/IV in 60/64 courses) and myelosuppression WHO grade III/IV in 15 courses. Neurotoxicity occurred in 3 patients and nephrotoxicity in 1 patient. Alopecia occurred in 12 patients. Tachycardia and other low-grade heart toxicities were observed after 5 courses. Dose reduction was necessary because of severe myelosuppression in 4 courses and because of nephrotoxicity in 1 course. Delay of subsequent chemotherapy courses for more than 7 days was necessary after 13 courses and was always due to myelosuppression. The dose-limiting toxicity of combination chemotherapy with cisplatin and pirarubicin is myelosuppression. Response and survival rates are superior in patients with relapsed disease compared to patients with resistent ovarian carcinoma.Work was in part presented at the Deutsche Krebskongreß 1992. Berlin, Germany, and at the EORTC-NCI Meeting on New Drugs in Cancer Chemotherapy 1992, Amsterdam, The Netherlands     

Monoclonal antibodies against EGFR in non-small cell lung cancer

Blockade of the epidermal growth factor receptor (EGFR) by monoclonal antibodies is a strategy to improve outcome in patients with non-small cell lung cancer. Cetuximab, a chimeric anti-EGFR monoclonal antibody, has been studied in combination with different chemotherapy protocols in both phase II and phase III trials in patients with advanced NSCLC. In the phase III FLEX trial, cetuximab added to cisplatin/vinorelbine resulted in an absolute overall survival benefit of 1.2 months compared to the same chemotherapy alone in patients with advanced EGFR-expressing NSCLC. In the second phase III trial, cetuximab added to carboplatin plus paclitaxed failed to improve progression-free survival but suggested a survival benefit similar to that seen in the FLEX trial. However, the benefit in survival reached statistical significance only in the FLEX trial. A meta-analysis that included patients from four randomized trials confirmed the efficacy of cetuximab when added to chemotherapy. Thus addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced NSCLC. Matuzumab and panitumumab have also been evaluated in phase II trials. Necitumumab is currently evaluated in combination with chemotherapy in two randomized phase III trials.