Gemcitabine in advanced pancreatic cancer: a phase II trial.

The 5-year survival for pancreatic cancer is usually less than 5%, and no treatment has demonstrated consistent effect on patient survival and disease-related symptoms. Early studies with gemcitabine suggested a modest antitumor activity with significant improvement in disease-related symptoms. This phase II study reports the activity of gemcitabine on 33 consecutive patients with unresectable pancreatic carcinoma. Twenty-three patients had metastatic and 10 locally advanced unresectable disease. Twenty-six patients had not received any previous treatment and seven had received first-line chemotherapy with 5-fluorouracil. Gemcitabine 1,000 mg/m2 was administered intravenously in 30 minutes in the first cycle once weekly for up to 7 weeks followed by 1 week rest; then in subsequent cycles, once weekly for 3 of every 4-week cycle. Four patients obtained partial response (12%). Fifteen patients (45%) had stable disease with a median duration of 32 weeks (range: 16-75 weeks), and 14 patients experienced progressive disease. Median duration of response was 34.5 weeks (range: 19-50 weeks). Median survival was 33 weeks (range: 2-91 weeks). All 4 responding patients and 14 of 15 (93%) patients with stable disease had improvement in performance status and decrease in daily analgesic requirement. Toxicity was mild and mainly consisted of moderate and rapidly reversible myelosuppression. We conclude that gemcitabine chemotherapy was very well tolerated and determined a significant clinical improvement with modest antitumoral activity in patients with advanced pancreatic cancer.

A better therapeutic profile for the combination of mitomycin-C, ifosfamide and cisplatin (MIC) in advanced non-small-cell lung cancer: a useful dose-schedule modification.

BACKGROUND: In our previous experience with chemotherapy for non-small-cell lung cancer (NSCLC) the combination of mitomycin, ifosfamide and cisplatin (MIC) showed the highest activity in a three-arm randomized trial; the MIC regimen also yielded the most toxic effects, with 8% WHO grade 2-4 nephrotoxicity, 21% grade 3-4 leukopenia and 10% grade 3-4 thrombocytopenia. In that study cisplatin (120 mg/m2) was delivered on day 1 and ifosfamide and mitomycin on day 2. In an effort to reduce MIC toxicity a modified regimen was tested in a phase II trial: cisplatin 100 mg/m2 was given on day 2 and ifosfamide on day 1 with mitomycin. PATIENTS AND METHODS: From November 1993 to December 1995, 70 advanced NSCLC patients entered the trial. RESULTS: Twenty-nine of 70 patients achieved major response (41%) with 6 complete (9%) and 23 partial remissions (33%). We recorded 4% of WHO grade 3-4 anemia, and 2% of leukopenia and thrombocytopenia. CONCLUSION: We confirmed the activity of the MIC regimen in NSCLC, and the modified schedule seems to substantially improve the safety of the combination.

A three-week schedule of gemcitabine-cisplatin in advanced non-small-cell lung cancer with two different cisplatin dose levels: a phase II randomized trial.

BACKGROUND: To explore a new schedule of gemcitabine-cisplatin (GP) combination therapy using two different cisplatin doses in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From May to December 1997, 92 chemonaive patients entered the study and 88 (28 with locally advanced and 60 with disseminated NSCLC) were evaluable for response and toxicity (45 in arm A and 43 in arm B). Patients were randomly assigned to arm A or arm B. Gemcitabine 1000 mg/m2 was given on days 1-8 plus cisplatin 100 mg/m2 in arm A and cisplatin 70 mg/m2 in arm B on day 2 of every 21-day cycle. RESULTS: The overall response rates in arms A and B were 42% (95% confidence interval (CI): 27.8%-56.7%) and 47% (95% CI: 31.6%-61.5%), respectively. Median duration of response was 9.7 months (range 1.8 to 30.9 months; 13.1 and 9.5 months for arm A and B, respectively), and median survival was 12 months (range 0.2 to 31.1 months; 15.4 and 11.5 months for arm A and B, respectively). Major WHO grade 3-4 toxicities in arm A vs. arm B included: thrombocytopenia (23% vs. 17% of courses), leukopenia (15%, vs. 4% of courses), anemia (7% vs. 6% of courses), and nausea-vomiting (20% vs. 7% of patients). Grade 1-2 nephrotoxicity occurred in 20% of patients in arm A and in 7% of patients in arm B, with one grade 4 episode in arm A. Six patients discontinued treatment because of toxicities, 5 in arm A and I in arm B. CONCLUSIONS: Results of this trial indicate that both schedules are feasible and active, with a milder toxicity in the arm with the lower cisplatin dose.

Cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) is more active than 5-fluorouracil, doxorubicin and methotrexate (FAMTX) in advanced gastric carcinoma.

BACKGROUND: 5-Fluorouracil (5-FU), doxorubicin and methotrexate (FAMTX) and cisplatin, epirubicin, leucovorin and 5-FU (PELF) have both been reported to be superior to the combination 5-FU, doxorubicin and mitomycin C (FAM) in advanced gastric carcinoma. On the basis of the presence and dose intensity of the included agents, we hypothesised that PELF would be superior to FAMTX. PATIENTS AND METHODS: Two hundred patients with untreated advanced gastric carcinoma were randomised to receive PELF or FAMTX for a maximum of six cycles or until disease progression. RESULTS: The complete response (CR) rates to PELF and FAMTX were, respectively, 13% [95% confidence intervals (CI) 6% to 20%] and 2% (95% CI 0% to 5%; P = 0.003), and the objective response rates [CR plus partial response (PR) rates] 39% (95% CI 29% to 49%) and 22% (95% CI 13% to 30%; P = 0.009), thus significantly favouring the PELF combination. The survival rates after 12 months (30.8% versus 22.4%) and 24 months (15.7% versus 9.5%) were also higher among patients receiving PELF, but these differences were not statistically significant. The toxicities were qualitatively different but quantitatively similar. Both regimens seem to be feasible provided that careful patient monitoring is assured. CONCLUSIONS: PELF is significantly more active than FAMTX and deserves further research in the adjuvant setting.