Gemcitabine in low dose in prolonged infusion is a treatment with documented activity against a variety of tumors. We here report the first randomized trial to compare standard brief and low-dose ...prolonged infusion of gemcitabine.
Eligible patients had non-small cell lung cancer in stage IIIB (wet) or IV, Karnofsky performance status 100 to 70 (Eastern Cooperative Oncology Group 0–2), measurable disease, were chemonaïve and fulfilled the standard criteria for chemotherapy. In arm A (standard treatment), gemcitabine was given at 1250 mg/m2 in 20 to 30 minutes and in arm B (prolonged infusion) at 250 mg/m2 in 6 hours infusion. All patients received gemcitabine on days 1 and 8 and cisplatin at 75 mg/m2 on day 2 of a 3-week cycle for four cycles, followed by two cycles of gemcitabine as monotherapy.
A total of 249 patients (188 men and 61 women, median age 58 years) were randomized between arm A (125 patients) and arm B (124 patients). Adenocarcinoma (53.9%) was the predominant histologic type; 92% of patients were in stage IV. The two groups were balanced for prognostic factors; however, group A had fewer patients with significant weight loss and no patient with lung cancer as a second malignancy or after radiotherapy for brain metastases. Grade 3 or greater toxicity was rare: anemia in 0.8 and 3.2%, neutropenia in 21.6 and 22.6%, thrombocytopenia in 0 and 1.6%, and nausea/vomiting in 4 and 8.1% for arms A and B, respectively. Alopecia was seen in 54.5% of patients in arm B, as compared with 9.7% in arm A. No patient died of treatment-related toxicity. During cycle 5, 47.7% of patients in arm A and 60.7% in arm B reported improved well-being, as compared with the status before chemotherapy. Patients in arm A had no complete remission, 32.8% partial responses, 48% minimal responses or stable disease, 13.6% progressions, and 5.6% were not evaluable. For arm B, the corresponding figures are as follows: complete remission 0.8%, partial responses 46% (for overall response rate of 46.8%), minimal responses or stable disease 36.3%, progression 12.1%, and not evaluable 4.8%. Median progression-free survival was 5.5 and 6.0 months, median overall survival was 10.1 and 10.0 months, and 1-year survival was 46.6 and 41.1% for arms A and B, respectively. For the 71 patients with squamous carcinoma, arm B seems superior to arm A, as seen by the higher overall response rate (51.3 versus 35.5%), longer median progression-free survival (6.2 versus 4.9 months), and longer median survival (11.3 versus 8.5 months). However, because of the small number of patients, these differences did not reach the level of statistical significance.
In the treatment of advanced non-small cell lung cancer, gemcitabine in low dose in prolonged infusion in combination with cisplatin has low toxicity and has activity comparable with gemcitabine in higher dose in standard brief infusion. Low-dose gemcitabine may be preferred for incurable cancer among economically deprivileged patients. In addition, apparent superior activity against squamous carcinoma opens new perspectives and deserves further research.
After a favorable experience with gemcitabine at a low dose in a prolonged infusion in combination with cisplatin for advanced non-small-cell lung cancer, here, we present the results from a phase II ...trial for patients with malignant pleural mesothelioma. Eligible patients had biopsy-proven malignant pleural mesothelioma, were chemo-naive, Eastern Cooperative Oncology Group performance status 0–2, had normal hematopoietic liver and renal function, and gave informed consent. Treatment consisted of gemcitabine 250 mg/m in a 6-h infusion on days 1 and 8 and cisplatin at 75 mg/m on day 2 of a 3-week cycle for four cycles, followed by two additional cycles without cisplatin. Seventy-eight patients (58 men, 20 women; age 33–82 years, median 58) were recruited into the trial. The histologic types were as followsepitheloid 56 (71.8%); four sarcomatoid (5.1%); mixed 15 (19.2%); and mesothelioma, three not otherwise specified (3.8%). Grades 3–4 toxicity included two (2.6%) patients with anemia, 18 (23.1%) with neutropenia, and one with nausea/vomiting. Reversible thrombocytosis with platelets over 1000–10/l was recorded in 10 (12.8%) patients and grade 2 alopecia in 60 (76.9%). Four (5.1%) patients showed a complete response and 35 (44.9%) showed a partial response with a response rate of 39/78 (50%). Minimal response or stable disease was seen in 35 (44.9%), whereas only four (5.1%) patients progressed during treatment. Most patients reported symptomatic improvement with a higher or a stable quality of life score in 70 (89.7%) cases. The median progression-free survival was 8.0 months (confidence interval 6.9–9.0). The median overall survival was 17.0 months (confidence interval 14.7–19.2). One-year, two-year, and three-year survival rates were 67.3, 32.7, and 19.8%, respectively. Epitheloid histological type was the only statistically significant favorable prognostic factor for progression-free survival and overall survival. Because of the acceptable toxicity, remarkable activity, and reasonable cost, this treatment should be further explored.
Background. Glioblastoma is the most common primary brain tumour. It has a poor prognosis despite some advances in treatment that have been achieved over the last ten years. In Slovenia, 50 to 60 ...glioblastoma patients are diagnosed each year. In order to establish whether the current treatment options have any influence on the survival of the Slovenian glioblastoma patients, their data in the period from the beginning of the year 1997 to the end of the year 2008 have been analysed.
Patients and methods. All patients treated at the Institute of Oncology Ljubljana from 1997 to 2008 were included in the retrospective study. Demographics, treatment details, and survival time after the diagnosis were collected and statistically analysed for the group as a whole and for subgroups.
Results. From 1997 to 2008, 527 adult patients were diagnosed with glioblastoma and referred to the Institute of Oncology for further treatment. Their median age was 59 years (from 20 to 85) and all but one had the diagnosis confirmed by a pathologist. Gross total resection was reported by surgeons in 261 (49.5%) patients; good functional status (WHO 0 or 1) after surgery was observed in 336 (63.7%) patients, radiotherapy was performed in 422 (80.1%) patients, in 317 (75.1%) of them with radical intent, and 198 (62.5 %) of those received some form of systemic treatment (usually temozolomide). The median survival of all patients amounted to 9.7 months. There was no difference in median survival of all patients or of all treated patients before or after the chemo-radiotherapy era. However, the overall survival of patients treated with radical intent was significantly better (11.4 months; p < 0.05). A better survival was also noticed in radically treated patients who received additional temozolomide therapy (11.4 vs. 13.1 months; p = 0.014). The longer survival was associated with a younger age and a good performance status as well as with a more extensive tumour resection. In patients treated with radical intent, having a good performance status, and receiving radiotherapy and additional temozolomide therapy, the survival was significantly longer, based on multivariate analysis.
Conclusions. We observed a gradual increase in the survival of glioblastoma patients who were treated with radical intent over the last ten years. Good functional surgery, advances in radiotherapy and addition of temozolomide all contributed to this increase. Though the increased survival seems to be more pronounced in certain subgroups, we have still not been able to exactly define them. Further research, especially in tumour biology and genetics is needed.
We present experience from a phase II randomized clinical trial, comparing standard gemcitabine as monotherapy with low-dose gemcitabine in long infusion in a doublet with cisplatin at reduced dose ...for patients with non-small cell lung cancer (NSCLC) and who are unfit for standard platin-based chemotherapy. Eligible patients had microscopically confirmed NSCLC in stage IIIB (wet) or IV, were chemo-naive, and were in poor performance status or presented with significant comorbidity. Standard treatment with gemcitabine, 1250 mg/m in 20–30 min on days 1 and 8 as monotherapy (arm A) was compared with low-dose gemcitabine in long infusion (200 mg/m in 6 h on day 1) and cisplatin at 60 mg/m on day 2 (arm B). Both treatment schedules were repeated every 3 weeks until disease progression, unacceptable toxicity, or to a maximum of six cycles. A total of 112 patients (83 male, 29 female, median age 66 years) were randomized between arm A (57 patients) and B (55 patients). The two groups were balanced for prognostic factors. Fifty-three patients in arm A and 52 in arm B received at least one application of chemotherapy and were evaluable for toxicity and response. The median number of cycles was four and five for arms A and B, respectively. Except for grade 3 anemia (one patient in arm A and two in arm B), no other major toxicity was seen. Regarding response to treatment, arm B was superior1 complete response and 13 partial remissions (response rate 26.9%) as compared with five partial remissions (response rate 9.4%) in arm A (P<0.01). The median time to progression was 3.8 and 5.6 months, and the median survival was 4.3 and 6.8 months for arms A and B, respectively (P<0.05). Treatment with low-dose gemcitabine in long infusion and cisplatin at reduced dose has very low toxicity, is effective, was found to be superior to monotherapy with gemcitabine in standard doses, and is suitable for patients with NSCLC who cannot tolerate a standard platin-based doublet.
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