[Show abstract][Hide abstract] ABSTRACT: Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor.
Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m(2), on days 1 and 5], epirubicin [30 mg/m(2), days 1 and 5], L-leucovorin [100 mg/m(2), days 1-4], and 5-fluorouracil [300 mg/m(2), days 1-4] in a hospital setting. Frequencies and severity of adverse events were determined. Overall survival (OS) and disease-free survival (DFS) were compared between the treatment arms using Kaplan-Meier analysis and a Cox proportional hazards regression model. All statistical tests were two-sided.
From January 1995 through September 2000, 258 patients were randomly assigned to chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were well balanced between the two arms. Among those who received chemotherapy, grade 3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of patients, respectively. After a median follow-up of 72.8 months, 128 patients (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity-related. Relative to treatment with surgery alone, adjuvant chemotherapy did not increase disease-free survival (hazard ratio [HR] of recurrence = 0.92; 95% confidence interval [CI] = 0.66 to 1.27) or overall survival (HR of death = 0.90; 95% CI = 0.64 to 1.26).
Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival. The estimated effect of chemotherapy (10% reduction in the hazard of death or relapse) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents.
[Show abstract][Hide abstract] ABSTRACT: The aim of this paper is to analyze the costs of chemotherapy-induced nausea and vomiting (CINV) in Italy.
In this prospective observational study at seven public oncology centers, incidence and intensity of CINV daily for 8 days after chemotherapy in consecutive patients receiving cisplatin-containing chemotherapy were recorded. All costs related to CINV (direct medical, direct nonmedical, and indirect) were recorded (in 2003 euros).
A total of 172 patients were enrolled; cost data were available for 168 patients. Thirty-seven percent of patients experienced acute CINV, and 57% experienced delayed CINV; 39% achieved total control, defined as no nausea, vomiting, or rescue therapy. Mean per-patient costs of acute and delayed CINV were 30.03 euro from the hospital perspective, 4.9 euro from the patient perspective, and 26.85 euro from the National Health Service (NHS) perspective. Costs of CINV were highly variable among oncology centers, largely because of differences in procedures for preventing delayed CINV. These costs were four times higher when antiemetic drugs were prescribed and paid for by the NHS than when antiemetic prophylaxis was provided directly from hospital pharmacies. Moreover, in the delayed phase, the NHS incurred a 94% increase in costs for patients without total control. Overall costs for patients who did not experience total control of CINV were 35.57 euro higher than for those who did (85% increase).
Costs of CINV for the Italian NHS could be reduced if hospitals furnished antiemetic prophylaxis directly to patients. Better control of both acute and delayed CINV would improve patient well-being as well as reduce the budgetary impact of CINV in Italy.
Supportive Care Cancer 02/2007; 15(1):31-8. DOI:10.1007/s00520-006-0094-x · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer of the testis is a relatively rare disease, accounting for about 1% of all cancers in men. Cryptorchidism is the only confirmed risk factor for testicular germ cell tumour. The majority of GCT are clinically detectable at initial presentation. Any nodular, hard, or fixed area discovered in the testis, must be considered neoplastic until proved otherwise. The appropriate surgical procedure to make the diagnosis is a radical orchidectomy through an inguinal incision. Many GCT produce tumoural markers (AFP, HCG, LDH), who are useful in the diagnosis and staging of disease; to monitor the therapeutic response and to detect tumour recurrence. In 1997 a prognostic factor-based classification for the metastatic germ cell tumours was developed by the IGCCCG: good, intermediate and poor prognosis, with 5-year survival of 91, 79 and 48%, respectively. GCT of the testis is a highly table, often curable, cancer. Germ cell testicular cancers are divided into seminoma and non-seminoma types for treatment planning because seminomatous testicular cancers are more sensitive to radiotherapy. Seminoma (all stages combined) has a cure rate of greater than 90%. For patients with low-stage disease, the cure approaches 100%. For patients with non-seminoma tumours, the cure rate is >95% in stages I and II; it is approximately 70% with standard chemotherapy and resection of residual disease, if necessary, in stages III and IV. Minimum guidelines for clinical, biochemical, and radiological follow-up have been reported by ESMO in 2001.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
PELF is significantly more active than FAMTX and deserves further research in the adjuvant setting.
Annals of Oncology 09/2003; 14(8):1258-63. DOI:10.1093/annone/mdg329 · 6.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
American Journal of Clinical Oncology 07/2001; 24(3):296-8. DOI:10.1016/S0959-8049(97)86176-X · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
Results of this trial indicate that both schedules are feasible and active, with a milder toxicity in the arm with the lower cisplatin dose.
Annals of Oncology 11/2000; 11(10):1295-300. DOI:10.1023/A:1008334610955 · 6.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
From November 1993 to December 1995, 70 advanced NSCLC patients entered the trial.
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.
We confirmed the activity of the MIC regimen in NSCLC, and the modified schedule seems to substantially improve the safety of the combination.
Annals of Oncology 08/1997; 8(7):709-11. DOI:10.1023/A:1008277604261 · 6.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Controversies exist regarding the classification of the emetogenic potential of chemotherapeutic agents such as taxanes, gemcitabine and irinotecan and the antiemetic prophylaxis for acute emesis to be administered. Instead, no prophylaxis for delayed emesis has been suggested. A prospective, observational study was carried out in 103 Italian oncological centers to evaluate the prescriptions of antiemetics and the incidence of nausea and vomiting in patients submitted to these chemotherapy agents. Two hundred and nine patients treated with taxanes, 300 with gemcitabine and 93 with irinotecan were evaluated. For the prophylaxis of acute emesis a 5-HT3 antagonist alone or in combination with a corticosteroid was administered to 86.6% of patients receiving taxanes, to 59.3% of those receiving gemcitabine and to 96.8% of those submitted to irinotecan. 20% to 40% of patients received antiemetic prophylaxis for delayed emesis. In taxane-treated patients the incidence of acute vomiting and nausea was 6.2% and 27.3%, respectively, while in gemcitabine- and irinotecan-treated patients it was 6.0/33.4% and 17.9/58.9%, respectively. In conclusion, the study showed that almost all patients received prophylaxis for acute emesis and that there is overprescription of 5-HT3 antagonists. The incidence of acute emesis is low; therefore, randomized clinical trials are necessary to verify the utility of prophylaxis and to find the best antiemetic treatment.