P. E. Postmus

A phase II study of oral etoposide in elderly patients with small cell lung cancer.

Thirty five previously untreated patients with small cell lung cancer older than 70 years were treated with oral etoposide (800 mg/m2 over five consecutive days) every four weeks. Twenty two patients had extensive disease and 13 limited disease. The overall response rate was 71%. The median survival for patients with limited diseases was 16 (range 6-32) months and for patients with extensive disease nine (range 4-17) months. There was mild haematological toxicity and alopecia but no major toxicity. It is concluded that etoposide in this dose regimen is an effective and well tolerated treatment for elderly patients with small cell lung cancer.

Recombinant interferon alpha-2b in patients with metastatic apudomas: effect on tumours and tumour markers.

Malignant carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid are tumours with similar clinical features. In patients with unresectable or metastatic tumours leukocyte interferon (IFN) and recombinant human (rh) IFN have demonstrated efficacy. Twenty-four evaluable patients with progressive tumours were treated with 2.5 megaunits rh IFN alpha-2b, administered once daily subcutaneously, for a median duration of 7 months (range 0.5-37+). Two carcinoid patients demonstrated a response in tumour size, 80% showed stable disease (SD). Sixty percent of the carcinoid patients with elevated urinary 5-hydroxyindoleacetic (5-HIAA) levels reached a biochemical partial response of the urinary 5-HIAA levels (median duration 13.5 months). In the patients with an islet cell or medullary tumour and an elevated tumour marker, the marker did not further increase. Of the 12 carcinoid patients evaluable for a symptomatic response, ten (83%) experienced a relieve of symptoms. IFN alpha-2b dose reduction or discontinuation due to toxicity was necessary in three and ten patients, respectively. No neutralising IFN alpha-2b antibodies developed despite prolonged treatment. In conclusion, IFN alpha-2b had a beneficial effect in patients with progressive tumours, while long-term IFN alpha-2b treatment did not augment neutralising antibodies. In view of the IFN alpha-2b-related toxicity, administration of IFN alpha-2b on alternating days may be preferable.

Cyclophosphamide and VP 16-213 with autologous bone marrow transplantation. A dose escalation study

In 13 patients with therapy-resistant solid tumors the feasibility of high-dose cyclophosphamide (7 g/m2) in combination with increasing doses of VP 16-213 with autologous bone marrow transplantation was studied. Dose-limiting extramedullary toxicity appeared to be mucositis and occurred after 2.5 g/m2. Two toxic deaths were observed in patients older than 55 yr. Responses were seen in eight out of nine evaluable patients. Two patients with ovarian cancer still have no signs of disease progression after 12+ months. High-dose cyclophosphamide (7 g/m2) can be combined with VP 16-213 1.5 g/m2 without important extramedullary toxicity. Age is probably a limiting factor for this kind of therapy.

Sarcoid reaction mimicking intrathoracic dissemination of testicular cancer

The close observation of patients treated for testicular cancer led to the suspicion of intrathoracic and/or mediastinal metastases on radiologic examination in a number of patients without other evidence of relapse. This report presents two patients with combined seminomatous and nonseminomatous germ cell tumors with isolated sarcoid reactions of hilar and interlobular lymph nodes, detected concomitant with diagnosis and 12 months after diagnosis, respectively. Histologic examination appears to be imperative in these cases to avoid unnecessary chemotherapy.

High-dose etoposide for meningeal carcinomatosis in patients with small cell lung cancer

INTRODUCTION IN A high percentage of SCLC patients, central nervous system (CNS) metastases are found and this usually results in considerable morbidity and mortality [ 11. This is especially the case in patients with meningeal carcinomatosis (MC). The incidence of MC in SCLC has been reported to be between 5 and 18%. With prolongation of survival , the chance of MC becoming symptomatic is rapidly increasing [ 11. The results of therapy for this devastating form of metastatic disease have been rather poor. After high-dose cyclophosphamide and etoposide with autologous bone marrow transplantation [2] and in a phase I study of etoposide [3], favourable responses of brain metastases from SCLC were found. In this report we describe the effect of highdose etoposide (HDE) in five patients with MC from SCLC.

Surgical resection for small cell carcinoma of the lung: a retrospective study.

BACKGROUND--A retrospective review was undertaken of the survival of 21 patients with histologically proven small cell carcinoma of the lung resected between 1977 and 1991. METHODS--Twenty one patients (20 men) of median age 60 (range 44-73) years underwent surgical resection. Patients were subjected to standard clinical staging procedures. Preoperative diagnosis was small cell carcinoma of the lung in 13, non-small cell lung cancer in one, and uncertain in seven patients. Clinical staging was stage I disease in 11 and stage II in 10 patients. RESULTS--Resection included pneumonectomy in 12 cases, lobectomy in eight, and one wedge resection. Resection was complete in 16 patients. Postoperative histopathological examination confirmed small cell carcinoma of the lung in 19 specimens and mixed small cell and non-small cell carcinoma of the lung in two. Pathological staging was stage I in 11, stage II in three, and stage III in seven patients. The final pathological diagnosis of the resected specimens (n = 18) was atypical carcinoid in one, pure small cell carcinoma of the lung in 15, and mixed small cell and non-small cell carcinoma of the lung in two patients. Fourteen patients also received chemotherapy and 10 received prophylactic cranial irradiation postoperatively. Excluding the patient with a final diagnosis of atypical carcinoid, the median survival (n = 20) was 29 months (range two to 133+). Median survival for patients with pathological stage I and II disease (n = 13) was 40 months (range nine to 133+) and for patients with pathological stage III disease (n = 7) 20 months (range two to 116+). The median disease free survival was 23 months. Eleven patients relapsed between two and 101 months. There was no advantage for those patients who received postoperative chemotherapy. CONCLUSION--Curative resection offers the best chance for long term survival in patients with small cell carcinoma of the lung with very limited stage disease.

Autologous cryopreserved platelets and prophylaxis of bleeding in autologous bone marrow transplantation

SummaryAutologous platelets were harvested and cryopreserved in eight consecutive patients elected for ablative chemotherapy and autologous bone marrow transplantation (ABMT) for solid malignancy. There was a 19% loss in platelet count after the freeze thaw and wash procedure; with an in vitro functional loss of 40–60%. No correlation could be found for individual platelet transfusions between in vitro functional tests and in vivo recovery. Six consecutive patients received a total of 16 autologous platelet transfusions in the aplastic phase of ABMT. No bleeding was observed during the study period and there was no CMV infection in the recipients. While improvement in freezing and subsequent handling is desirable, autologous cryopreserved platelets can safely be used for the prophylaxis of bleeding during aplasia in patients treated with ABMT.

A dose and schedule finding study of gemcitabine and etoposide in patients with progressive non-small cell lung cancer after platinum containing chemotherapy

BACKGROUND Combination chemotherapy improves survival in patients with disseminated non-small cell lung cancer (NSCLC). Gemcitabine is active against NSCLC and etoposide has an additive effect in vitro. We describe a dose finding study for the combination of these drugs. PATIENTS AND METHODS NSCLC patients progressive after chemotherapy received gemcitabine (1000 mg/m2 days 1, 8, 15) and one of five etoposide schedules in doses ranging from 60 to 100 mg/m2 per day administered on days 1-3 (schedules 1-2) or 8-10 (schedules 3-5). RESULTS 23 patients (median age 59 years) were entered. Number of patients and cycles evaluable for toxicity was 22 and 75. Non-hematological toxicity was mild. In cycle 1 leukocytopenia grade III/IV was observed in 33 and 56% of the patients treated with etoposide 60 and 80 mg/m2 days 1-3 and in 50% treated with etoposide 60 and 80 mg/m2 days 8-10. During cycle 1 thrombocytopenia grade III/IV was observed in 0, 33, 0 and 33% of these patients, respectively. Both patients treated at etoposide 100 mg/m2 days 8-10 experienced febrile leukocytopenia. During cycle 1 single doses of gemcitabine were administered as planned more frequently in patients receiving etoposide 80 mg/m2 per day on days 8-10 compared to etoposide days 1-3 (83 versus 70%). Postponement of combination gemcitabine and etoposide was not necessary. The overall response rate was 21% (95% confidence interval 3-39%) with a median duration of 7.5 + months in this dose finding study. CONCLUSIONS Combined gemcitabine etoposide is feasible in patients with progressive NSCLC. The optimal combination was gemcitabine 1000 mg/m2 per day on days 1, 8 and 15 and etoposide 80 mg/m2 per day on days 8-10 of each 28-day cycle. The response rate of 21% warrants further investigation in patients with advanced NSCLC.

Small cell lung cancer in the elderly. Factors influencing the results of chemotherapy: a review

In this review we will discuss some aspects of chemotherapy in elderly patients with cancer, with special emphasis on SCLC

NO NARCOSIS FOR BONE-MARROW HARVEST IN AUTOLOGOUS BONE-MARROW TRANSPLANTATION

SummaryA prospective study with mild general analgesia and sedation together with local anesthesia during bone marrow harvest was performed. Thirty-one patients underwent 33 bone marrow collections. Pretreatment consisted of 100 mg meperidine i.m. and 20 mg diazepam i.m. 1 h before start of procedure. Eight patients got additional meperidine and diazepam during the procedure, all patients got lidocaine 1% locally. A mean volume of 1.321 was obtained with 42.5 punctures. Twenty-two patients had no complications, 4 vomited, 4 had easily correctable hypotension of short duration, one got oxygen for cyanosis of short duration. Acceptance was good in 23 patients, in 6 reasonably well, in two bad. Only one patient experienced pain problems, due to suction. Anxiety was no major problem due to good information before the procedure and mild sedation.This form of anesthesia for bone marrow collection is a safe procedure, it is generally well accepted by the patient and it can be performed on an out-patient basis.