Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study.

Cancer of unknown primary site (CUP) represents up to 5% of all cancer diagnoses and is associated with poor survival. We have performed a prospective multicentre phase 2 trial to evaluate efficacy and toxicity of the combination of gemcitabine (G) and carboplatin (C) for patients with CUP. Patients with histologically confirmed metastatic carcinoma in which the primary site of cancer was not evident after prospectively designated investigation and who had ECOG performance status 0-2 were treated with G 1000 mg m(-2) intravenously (i.v.) days 1 and 8, and C AUC 5 i.v. on day 8 every 3 weeks to a maximum of nine cycles. The primary end points were response rate, and toxicity, with secondary end points of progression-free survival and overall survival. Fifty-one (23 male, 27 female) patients were enrolled (one patient ineligible), with a median age of 69 years (range 41-83 years). Fifty patients were evaluable for toxicity and 46 patients were evaluable for efficacy. The overall response rate to the GC regimen was 30.5%. With a median follow-up of 24 months, the median progression-free survival was 18 weeks (4.2 months) and the median overall survival was 34 weeks (7.8 months). The frequency of grade 3 or 4 toxicity was low. Nausea/vomiting was the most common side effect, but was usually only mild in severity. Uncomplicated neutropenia (14%), thrombocytopenia (10%) and anaemia (8%) were the most common causes of grade 3-4 toxicity. The regimen was very well tolerated, particularly in the elderly. The GC regimen is an active regimen in CUP with excellent tolerability and should be considered particularly for elderly patients with CUP.

Weekly oral paclitaxel as first-line treatment in patients with advanced gastric cancer.

BACKGROUND: Pharmacokinetic study has shown that co-administration of cyclosporin A (CsA), which acts as a P-glycoprotein (P-gp) and CYP-3A blocker, resulted in an 8-fold increase in the systemic exposure of oral paclitaxel. Two doses of oral paclitaxel on 1 day in combination with CsA resulted in higher systemic exposure than single dose administration. PATIENTS AND METHODS: In this phase II study, chemonaïve patients with advanced gastric cancer received oral paclitaxel weekly in two doses of 90 mg/m(2) on the same day; CsA (10 mg/kg) was given 30 min before each dose of oral paclitaxel. RESULTS: In 25 patients, the main toxicities were: nausea CTC grade 2/3, 10 patients (40%); vomiting grade 2/3, 4 patients (20%); diarrhea grade 2/3, 6 patients (24%); neutropenia grade 3/4, 5 patients (20%). In the 24 evaluable patients, eight partial responses were observed, resulting in an overall response rate (ORR) of 33% [95% confidence interval (CI) 18% to 52%]. Eleven patients had stable disease (46%) and 5 patients showed progressive disease (21%). The ORR in the total population was 32% (95% CI 17% to 50%). The median time to progression was 16 weeks (95% CI 9-22). Pharmacokinetic analyses revealed that the mean area under the plasma concentration-time curve (AUC) of orally administered paclitaxel (+/- standard deviation) was 3757.6 +/- 939.4 ng.h/ml in week 1 and 3928.4 +/- 1281 ng.h/ml in week 2. The intrapatient variability in the AUC was 12%. CONCLUSIONS: Oral paclitaxel in combination with CsA is both active and safe in chemonaïve patients with advanced gastric cancer. Toxicities were mainly gastrointestinal.

Multicenter phase II study of gemcitabine in previously untreated patients with advanced epithelial ovarian cancer.

Gemcitabine has activity in advanced ovarian cancer, with responses in platinum-resistant disease. This study assessed the activity of gemcitabine in previously untreated patients with advanced epithelial ovarian cancer. All patients had histologically verified invasive epithelial ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease and no prior chemotherapy. Patients received gemcitabine 1250 mg/m(2) on days 1, 8 and 15 of a 28-day cycle. Radiological response was assessed after two cycles. Between December 1992 and October 1995, 35 patients were enrolled. Of 33 evaluable patients, there was one complete response and five partial responses, for an overall response rate of 18% (95% confidence interval 7-36%). Forty-two percent of patients had a greater than 50% decrease in their CA-125 levels. Of the 25 patients who received platinum-based chemotherapy following treatment with gemcitabine, 12 achieved an overall response rate of 48%. Toxicity was mild, with two episodes of WHO grade 4 neutropenia (not associated with fever) and two episodes of grade 4 thrombocytopenia (not associated with bleeding). Gemcitabine has single-agent activity for poor-prognosis patients with advanced ovarian cancer. Similar results with subsequent platinum-based therapy indicate a lack of cross-resistance. This, combined with gemcitabine's favorable toxicity profile, warrants testing in comparative trials.

Treatment of invasive thymoma with single-agent ifosfamide.

PURPOSE: To evaluate single-agent ifosfamide in the treatment of invasive thymoma. PATIENTS AND METHODS: Fifteen patients (eight male and seven female) with histologically confirmed invasive thymoma were treated. The median age was 48 years (range, 23 to 76 years). Four patients had stage III disease, seven patients had stage IVa disease, and four patients had stage IVb disease. The most common histologic type was lymphoepithelial. Seven patients had received prior treatment, including one patient who received chemotherapy. Ifosfamide 1.5 g/m(2) was given on days 1 to 5, with mesna as a uroprotector. RESULTS: Thirteen patients were assessable for response. Five complete responses (38.5%; 95% confidence interval [CI], 17.7% to 64.5%) and one partial response (7.7%; 95% CI, 1.4% to 33.3%) were seen. The median duration of complete response was 66+ months (range, 25 to 87 months), and the estimated survival rate 5 years after ifosfamide treatment was 57% (SE, 32% to 79%). The most frequent toxicities were nausea, vomiting, and leucopenia, but these were well tolerated. CONCLUSION: Single-agent ifosfamide possesses significant activity against invasive thymoma and is comparable to currently used combination regimens. The inclusion of ifosfamide in combination therapy, particularly in place of cyclophosphamide in regimens such as cisplatin, doxorubicin, and cyclophosphamide, needs to be evaluated.

A phase II trial of cisplatin and interferon alpha 2b in patients with advanced bladder cancer.

Twenty-two patients with advanced transitional cell bladder cancer were treated in a phase II trial exploring the possible synergy of cisplatin and interferon alpha 2b. Of the 20 evaluable patients, 7 (35%) had a partial response to the treatment, and only 6 patients were able to complete the full planned six cycles of treatment. Response rates, duration of responses, and overall survival of our patients are not superior to those expected by cisplatin alone.

Salvage radiotherapy following chemotherapy failure in Hodgkin's disease--what is its role?

Radiotherapy is rarely used as salvage therapy following chemotherapy failure in Hodgkin's disease. Analysis of our experience identified only 11 cases from over 400 patients treated, and data from other centres are similarly sparse. Three (43%) of 7 patients with relapse confined to nodal sites were salvaged with radiotherapy alone. Actuarial relapse free survival at 5 years was 27% (+/- 12 SE) with survival 45% (+/- 15 SE). These data were then combined with four other detailed series in the literature to delineate the patient and disease characteristics of 60 patients, and better assess the role of salvage radiotherapy. This confirms that radiotherapy has an important role in salvaging a small proportion of cases, who can be spared the risk of more aggressive regimens, such as high dose chemotherapy. Patients with relapse confined to one or two nodal sites, and having a disease free interval greater than 12 months, have the best prospects for salvage. Initial stage IV disease seems to have little bearing, provided relapse is confined to nodal sites.

Combination chemotherapy with epirubicin, cisplatin and 5-fluorouracil for the palliation of advanced gastric and oesophageal adenocarcinoma.

The palliative efficacy of laser therapy with combination chemotherapy (cisplatin, epirubicin and continuous infusion of 5-fluorouracil) was assessed in 34 patients with inoperable gastro-oesophageal cancer. Comparison was made with a group of 30 patients treated previously by laser alone. Twenty patients responded to chemotherapy. There was a significant improvement in dysphagia, as measured by a decreased laser requirement to maintain satisfactory swallowing. In this non-randomized prospective phase II trial, palliation was attained and some responses were long-lasting (median duration of response 8.7 (range 2.3 to more than 29.2) months).

Lead poisoning--a family study.

OBJECTIVE: A family study is used to highlight the varied manifestations of lead poisoning and difficulties in diagnosis and treatment. CLINICAL FEATURES: A 42-year-old Italian woman with a known beta-thalassaemia trait presented with a two-year history of disabling pains and symptomatic anaemia, which were found to be caused by lead poisoning. INTERVENTION AND OUTCOME: Screening for lead poisoning among her immediate family members identified two others with different manifestations of plumbism. All three needed active chelating, which resulted in resolution of their symptoms. CONCLUSIONS: The similar haematological findings of beta-thalassaemia and lead poisoning may lead to a delay in diagnosis and treatment of lead poisoning when these two conditions coexist.