Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer.

BACKGROUND: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. PATIENTS AND METHODS: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m(2), day 1) and vinorelbine (25 mg/m(2) on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m(2), followed by 250 mg/m(2) weekly thereafter). RESULTS: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. CONCLUSION: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone.

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer.

Anthracyclines are amongst the most active drugs in the treatment of breast cancer. Stealth liposomal doxorubicin (Caelyx, Doxil, Alza Pharmaceuticals Inc.) is a promising new agent under investigation for the treatment of breast cancer and other solid tumours. The liposomal encapsulation alters drug pharmacokinetics and leads to a marked change in toxicity profile compared to non-liposomal doxorubicin. The results of recently completed and ongoing clinical trials in breast cancer are reviewed.

Management of elderly patients with lung cancer.

Cancer management in the older patient is a growing concern, particularly with the increasing geriatric population and the high incidence of cancer among these individuals. Incidence of lung cancer in particular is known to rise with age. This article reviews prognosis, treatment options, and decision-making issues for both clinician and patient with respect to both non-small-cell and small-cell lung cancer in this population. Research findings dealing with response rates, survival rates, and symptom control in this age group are reviewed for radiotherapy, surgery, and for various chemotherapy agents, including gemcitabine, the taxanes, vinorelbine, and the topoisomerase 1 inhibitors. Quality- of-life issues are also addressed.

Cerebral metastases in malignant mesothelioma: a case report.

A case of a 61-year-old man with metastatic malignant mesothelioma is described. Four months after diagnosis the patient commenced chemotherapy with liposomal doxorubicin as part of an EORTC phase II trial. He developed signs of intracerebral metastases after his fourth cycle of chemotherapy and died shortly after. Malignant mesothelioma is traditionally viewed as a disease that spreads locally but metastasizes rarely. We describe in detail this case and suggest that metastases in this disease are not as uncommon as originally proposed.

Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial.

PURPOSE: A multicenter phase II study to determine the activity and toxicity of Caelyx (Doxil; Sequus Pharmaceuticals Inc, Menlo Park, CA) in patients with metastatic breast cancer. PATIENTS AND METHODS: Seventy-one patients with stage IV breast cancer were treated with Caelyx at doses of 45 to 60 mg/m2 every 3 to 4 weeks for a maximum of six cycles. Twenty-eight patients had received prior chemotherapy with a nonanthracycline regimen. Fifty-two patients had disease at multiple sites. Hepatic and pulmonary disease were the predominant metastatic site in 50 patients. Response was assessable in 64 cases. RESULTS: Sixteen patients achieved a partial response and a complete response (overall response rate, 31%; (95% confidence interval, 20% to 43%). Twenty patients (31%) had stable disease on treatment. Neutropenia > or = grade 3 occurred in 10% of cycles (27% of patients) and mucositis > or = grade 3 in 10% of cycles (32% of patients). Significant alopecia was rare and routine prophylactic antiemetics were not required. At doses of 60 mg/m2 every 3 weeks, seven of 13 patients had > or = grade 3 skin toxicity; overall, this toxicity complicated 25% of treatment cycles. The incidence of > or = grade 3 skin toxicity was greatly reduced at doses of 45 mg/m2 every 4 weeks, occurring in five of 32 patients and affecting only 5% of 126 treatment cycles. CONCLUSION: Caelyx is an active agent in advanced breast cancer with a safety profile that differs markedly from nonliposomal doxorubicin. A regimen of 45 mg/m2 every 4 weeks was well tolerated in this cohort of women with advanced poor-prognosis breast cancer. The mild myelosuppression seen with this regimen would favor its use in combination chemotherapy.

Single-agent paclitaxel in advanced non-small cell lung cancer: single-center phase II study using a 3-hour administration schedule.

The efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered as a 3-hour infusion was investigated in a phase II study involving 21 patients with stage III/IV non-small cell lung cancer. The study included two quality of life assessments (the Hospital Anxiety and Depression Scale and the Rotterdam Symptom Checklist) to test their suitability for use in a future randomized phase III trial of paclitaxel and best supportive care versus best supportive care alone. Four (19%) of the 21 patients (95% confidence interval, 8% to 38%) achieved a partial response. The median time to disease progression for all patients entered was 19 weeks. Paclitaxel was well tolerated, with dose reduction required in only one patient because of arthralgia/myalgia. No dose reductions, delays, or discontinuations were required for hematologic toxicity. Completion and compliance with quality of life questionnaires was high, and these research tools proved to be acceptable for future use in phase III studies with paclitaxel.

Central venous catheter placement: extending the role of the nurse.

OBJECTIVE: To improve the quality of the percutaneous tunnelled central venous catheter placement service for patients being treated for malignant disease. DESIGN: A clinical nurse specialist was specially trained to insert percutaneous tunnelled central venous catheters according to predetermined guidelines. Catheters were inserted under local anaesthetic in the outpatient department or the ward. The quality of the service was analysed and compared with the pre-existing service provided by junior medical staff. SUBJECTS: Two hundred adult patients with malignant disease seen between January 1995 and January 1996 at the Christie Hospital Trust. MAIN OUTCOME MEASURES: Success of the procedure, insertion-related infection rates and waiting times compared to historical controls. RESULTS: The rate of failed insertions fell from 20% to 3% with a concomitant reduction in surgical referrals; for 97% of patients waiting time was reduced to less than one working day compared with 80% previously. Line-related infection rates in the first thirty days following insertion fell from 10 episodes per 72 lines inserted to two episodes per 200 lines inserted. CONCLUSIONS: Training and using a clinical nurse specialist has improved the quality of service and gives junior doctors more opportunity to become competent in the technique of central venous catheter placement. The introduction of guidelines has encouraged a standard approach that facilitates audit.

Post consolidation therapy for adult patients with acute myeloid leukaemia.

One hundred and sixteen adult patients aged 14-73 with previously untreated acute myeloid leukaemia received induction and consolidation chemotherapy with daunorubicin, cytosine arabinoside and thioguanine. Two novel approaches to post consolidation therapy have been investigated. Patients aged 50 years or less who had no suitable matched allogeneic donor were considered for autologous bone marrow transplantation (BMT) using bone marrow which had been cultured in vitro for 14 d. Patients over the age of 50 years with normal bone marrow cellularity and peripheral blood count were treated with a single oral dose of busulphan 100 mg/m2 (without BMT rescue) 3 months following the completion of consolidation therapy. Eighty-seven patients (75%) achieved a complete remission. Of 70 patients who completed consolidation therapy, 40 were aged less than or equal to 50 years and 30 were greater than 50 years. Forty-three patients went on to receive post consolidation therapy in first CR (autologous BMT 12, allogeneic BMT 7, busulphan therapy 24). The event-free survival at 4 years was 47% for autologous BMT, 34% for allogeneic BMT and 45% for busulphan-treated patients. The survival for the older cohort of patients who received post consolidation therapy with single dose busulphan therapy was encouraging, and this agent should be considered for future post consolidation strategies.

An analysis of prognostic factors in stage III and IV Hodgkin's disease treated at a single centre with MVPP.

Two hundred and twenty seven patients with stage IIIA-IVB Hodgkin's disease have been treated at a single centre with MVPP chemotherapy followed by radiotherapy to sites of previously bulk disease. The median follow up is 58 months. 119 patients (52%) had stage IV disease. Overall complete remission (CR) rate was 72%. Discriminant analysis of factors predictive for complete remission showed that low albumin was the only independent factor that predicted a significantly lower chance of CR. Overall five year survival was 73%. A Cox multivariate analysis demonstrated that age greater than 40 years, stage IV disease, presence of bulk disease, low serum IgG and male sex to be variables which independently predicted poorer prognosis in terms of overall survival. Stage IV and lymphocyte depleted or unclassified histologies were independently predictive for poorer progression-free survival. Patient weight greater than 70 kg and stage IV disease were adverse prognostic factors for relapse free survival. Results are compared to other published multivariate analyses of prognostic factors in advanced Hodgkin's disease.

Ifosfamide, doxorubicin and etoposide in small cell lung cancer patients with poor prognosis.

61 patients with small cell lung cancer in a poor prognosis group were treated with chemotherapy and with thoracic radiotherapy if they had 'limited stage' disease. No prophylactic cranial irradiation was given. Chemotherapy comprised doxorubicin 50 mg/m2 and ifosfamide 5 g/m2 with mesna on day 1, and etoposide 120 mg/m2 intravenously on days 1 and 2 and 240 mg/m2 orally on day 3. Treatment was repeated every 3 weeks for a maximum of six courses and no dosage reductions were allowed. Complete response rate in limited stage patients was 55% and 16% in extensive stage patients. The partial responses were 38% and 66% respectively. Overall median survival was 10.5 months with 2-year survival of 14%. The corresponding values for limited stage disease were 13 months and 16% and for extensive stage disease 8 months and 13%. Despite the addition of doxorubicin at a somewhat higher dosage than usual in this type of regimen and a policy of no dose reduction, toxicity was generally mild. There was, however, a 19% relapse rate in complete responders in the brain, apparently as the sole site of disease.

Double-blind placebo controlled study of vancomycin prophylaxis for central venous catheter insertion in cancer patients.

To assess whether vancomycin administration at the time of central venous catheter insertion would prevent catheter-related sepsis (CRS) in immunocompromised patients, 98 cancer patients were entered into a randomized placebo-controlled trial. Patients were stratified according to whether they were having therapy for acute leukaemia or undergoing bone-marrow transplantation (group A) or required chemotherapy for a solid tumour (group B). Eligible patients were randomized to receive either 500 mg vancomycin in 250 ml of 0.9% saline prior to catheter insertion followed by a further 500 mg infused via the established catheter, or the same regimen with 0.9% saline alone. In group A, there were 32 instances of CRS occurring in 20 of the 35 evaluable catheters (57%). Six catheters were removed because of CRS. No significant difference was found in the incidence of CRS between the two arms. Of the 37 evaluable catheters in group B, CRS occurred in 6 (16%), and none of the catheters required removal because of CRS. Again, no significant differences were found in the incidence of CRS between the patients given vancomycin or placebo. These findings indicate that the incidence of CRS is greater in patients who have more severe and prolonged immunosuppression and that vancomycin prophylaxis fails to reduce CRS in patients undergoing chemotherapy for malignant disease.