Gemzar-Gemcitabene

  • Interim analysis of a phase III trial. Triple- vs double-agent chemotherapy for advanced non-small-celllung cancer. Southern Italy Cooperative Oncology Group.
  • Gemcitabine/alimta in locally advanced or metastatic non-small-cell lung cancer.
  • Gemcitabine, paclitaxel, and carboplatin for advanced non-small-cell lung cancer.
  • Gemcitabine/carboplatin combination regimens: importance of dose schedule.
  • Combination chemoradiotherapy with gemcitabine: potential applications.
  • Advances in treatment of inoperable NSCLC: gemcitabine doublets--a promising alternative.
  • Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.
  • Second-line chemotherapy with paclitaxel, cisplatin and gemcitabine in pre-treated sensitive cisplatin-based patients with advanced non-small cell lung cancer.
  • Gemcitabine/cisplatin as induction therapy for stage IIIA N2 non-small-cell lung cancer.

Interim analysis of a phase III trial. Triple- vs double-agent chemotherapy for advanced non-small-celllung cancer. Southern Italy Cooperative Oncology Group.

Comella P

In our previous phase I/II studies, both the cisplatin (Platinol), gemcitabine (Gemzar), and vinorelbine (Navelbine) (PGV), andcisplatin, gemcitabine, and paclitaxel (Taxol) (PGT) regimens produced a median survival of approximately 1 year in patients with advanced non-small-cell lung cancer (NSCLC). The present phase III study compared the median survival of patients treated withthese triple-drug regimens to that of patients receiving cisplatin plus vinorelbine (PV) or cisplatin plus gemcitabine (PG). Accrual for thetrial began in 1997 and by December 1998, a total of 240 patients (stage IIIB, 98; stage IV, 142) had been enrolled. An interim survival analysis was performed in April 1999. Overall, 151 patients had died. The median survival rates of patients in the PGV, PG,and PV arms were 51, 42, and 35 weeks, respectively. At the time of this analysis, the median survival of patients in the PGT arm could not be assessed; however, the 1-year projected survival rate was 58%. At multivariate Cox analysis, the estimated risk of deathfor patients receiving PGV compared with those receiving PV was 0.35 (95% CI, 0.16-0.77, P = .0058). Overall response rateswere 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm, and 58% in the PGT arm. Severe neutropenia and vomiting were significantly more frequent in patients who received PV than in those who received PGV. The PV regimen produced a significantlyshorter survival compared with the PGV combination. Since this difference in survival complied with one of the early stopping rules,accrual in the PV arm was discontinued. Enrollment in the PGV, PG, and PGT arms is ongoing.

Oncology (Huntingt) 2000 Jul;14(7 Suppl 4):35-40

Gemcitabine/alimta in locally advanced or metastatic non-small-cell lung cancer.

Ettinger DS

Johns Hopkins Oncology Center, Baltimore, Maryland, USA. ettinger@welchlink.jhu.edu

The search for new combination chemotherapeutic regimens for the treatment of non-small-cell lung cancer is motivated not only by thedesire to increase the objective tumor response and survival rates, but also by the desire to reduce toxicity, decrease symptoms, and improve the psychological well-being of treated patients. At present, the overall phase II response rates with existing combinationchemotherapeutic regimens are approximately 15% to 30%, and the median survival rates are about 8 to 9 months. The median 1-yearsurvival rates are about 30% to 40%, while the 2-year survival rates are only about 10% to 15%. Thus, while we have made substantial progress in the treatment of this disease, the long-term outcome is still relatively bleak. This article reviews the results of aphase I trial with a new combination chemotherapeutic regimen (gemcitabine [Gemzar] and the novel antifolate, Alimta), and outlinesthe rationale for, and design of, an ongoing phase II trial.

Oncology (Huntingt) 2000 Jul;14(7 Suppl 4):49-52

Gemcitabine, paclitaxel, and carboplatin for advanced non-small-cell lung cancer.

Greco FA, Burris HA 3rd, Hainsworth JD

Sarah Cannon Cancer Center, Nashville, Tennessee, USA.

The purpose of this study was to evaluate the combination of gemcitabine (Gemzar), paclitaxel (Taxol), and carboplatin (Paraplatin) inpatients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients with stage IIIB or IV NSCLC wereincluded in this trial. A total of 69 patients from the phase II portion and 8 patients from the phase I portion were treated withgemcitabine 1,000 mg/m2 intravenously (i.v.) on days 1 and 8; paclitaxel 200 mg/m2 as a 1-hour infusion on day 1; and carboplatin atan area under the curve (AUC) dose of 5.0 i.v. on day 1. Treatment courses were repeated every 21 days. The phase II componentof the study was completed at 13 community-based practices within the Minnie Pearl Cancer Research Network. Of the 71 fullyevaluable patients, 34 had an objective response, for an overall response rate of 48%; 2 patients showed complete responses and 32patients had partial responses. A total of 25 (35%) patients were stable and 12 (17%) patients progressed. The median response duration was 6 months (range 3 to 14 months), and the median survival was 9.9 months, with a 1-year survival of 47% and a 2-year survival of 21%. These results show that the combination of gemcitabine, paclitaxel, and carboplatin is safe and effective; however, randomized phase III studies are needed to prove this regimen is superior to other regimens.

Oncology (Huntingt) 2000 Jul;14(7 Suppl 4):31-4

Oncology (Huntingt) 2000 Jul;14(7 Suppl 4):26-30

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Gemcitabine/carboplatin combination regimens: importance of dose schedule.

Gandara DR, Lau DH, Lara PN Jr, Edelman MJ

University of California, Davis Cancer Center, Sacramento, USA. david.gandara@ucdmc.ucdavis.edu

[Medline record in process]

Platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), in combination with a number of new chemotherapeutic agents, have demonstrated improved response or survival compared to cisplatin alone or older platinum-based regimens. Gemcitabine (Gemzar)-platinum combinations are of particular interest because of their interactive mechanisms of action, demonstrated preclinical synergism, and the single-agent activity of gemcitabine. Indeed, gemcitabine and cisplatin regimens have proven to be among the most efficacious in the palliative treatment of advanced non-small-cell lung cancer. In view of the reduced nonhematologic toxicities associated with the platinum analogue, carboplatin, several combinations of new agents and carboplatin have been developed and incorporated into clinical practice. This article describes recent clinical trials evaluating gemcitabine plus carboplatin, and the impact of the dosing schedule on the feasibility and tolerability of this combination.

Oncology (Huntingt) 2000 Jul;14(7 Suppl 4):20-5

Combination chemoradiotherapy with gemcitabine: potential applications.

Choy H

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

[Medline record in process]

Gemcitabine (Gemzar) is a novel deoxycitidine drug that has demonstrated promising single-agent activity in non-small-cell lung cancer and has been proven to be a potent radiosensitizer. Although the exact mechanism of the radiosensitizing effect is unknown, several studies have focused on the drug's effect on deoxyadenosine triphosphate (dATP) pool depletion or cell-cycle manipulation. A number of trials have evaluated this feature of gemcitabine by combining chemotherapy and radiation in various doses and schedules, and those studies are described in this article. Gemcitabine appears to be a promising agent to be combined with radiation therapy. However, further clinical trials are needed to define optimal doses, toxicity, and efficacy.

Oncology (Huntingt) 2000 Jul;14(7 Suppl 4):7-14

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Advances in treatment of inoperable NSCLC: gemcitabine doublets--a promising alternative.

Cappuzzo F, Lima CM, Sherman CA, Green MR

Division of Hematology/Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, USA.

[Medline record in process]

Gemcitabine (Gemzar) was originally approved for use in combination with cisplatin (Platinol) for the treatment of advanced non-small-cell lung cancer (NSCLC). Research began to focus on combining gemcitabine with newer drugs, such as carboplatin (Paraplatin), vinorelbine (Navelbine), the taxanes, and the camptothecins, when it became clear that these agents had potentially increased efficacy and fewer side effects than the standard treatment. This article will briefly review the original experience with the gemcitabine/cisplatin doublet and then examine the experience to date with non-cisplatin-based gemcitabine doublet combinations in the treatment of advanced NSCLC.

Br J Cancer 2000 Aug;83(4):447-53

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Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.

Anderson H, Hopwood P, Stephens RJ, Thatcher N, Cottier B, Nicholson M, Milroy R, Maughan TS, Falk SJ, Bond MG, Burt PA, Connolly CK, McIllmurray MB, Carmichael J

Wythenshawe Hospital, Manchester, UK.

Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (> or = 25%) improvement in SS14 score between baseline and 2 months sustained for > or =4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters.The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t-test). A sustained (> or = 4 weeks) improvement (> or =25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84) for BSC patients, and 1 -year survival was 25% for gemcitabine + BSC and 22% for BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients received palliative radiotherapy. The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone. These improvements in patient-assessed QL were significant in magnitude and were sustained.

Anticancer Res 2000 May-Jun;20(3B):2229-33

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Second-line chemotherapy with paclitaxel, cisplatin and gemcitabine in pre-treated sensitive cisplatin-based patients with advanced non-small cell lung cancer.

Rosati G, Rossi A, Nicolella G, Panza N

Division of Medical Oncology, S. Carlo Hospital, Potenza, Italy. rosatiger@yahoo.com

BACKGROUND: To investigate the safety and effectiveness of the combination of paclitaxel, cisplatin and gemcitabine as second-line in patients with advanced non-small cell lung cancer (NSCLC) sensitive to first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: From June 1997 to December 1998, 26 patients with stage IIIB or IV NSCLC received paclitaxel 125 mg/m2, as a one-hour infusion, followed by cisplatin 50 mg/m2 and gemcitabine 1000 mg/m2, intravenously, on day 1 and 8, every 3 weeks. Twenty-three patients were male; the median age was 59 years (range 44-70); The Eastern Cooperative Oncology Group performance status was 0 to 1 in 88% of patients; 16 patients had stage IV disease and 7 patients had 3 or more sites of disease. The predominant histology was adenocarcinoma in 14 patients. Prior treatment involved cisplatin plus vinorelbine in 14 patients and cisplatin plus mitomycin C plus vindesine in 12 cases. RESULTS: Seven (27%; exact 95% confidence limits: 11.6-47.8%) patients achieved a partial response to treatment whilst 7 (27%) had stable disease. The median duration of response was 22 weeks (range, 18 to 34 weeks). The median overall survival was 24 weeks (range, 8 to 36 weeks). The main toxicities were: grade 3-4 neutropenia in 9 (34%) patients; grade 2-3 peripheral neuropathy in 10 (38%); and grade 2-3 asthenia in 15 (57%) cases. CONCLUSION: The paclitaxel, cisplatin and gemcitabine combination is active as a second-line regimen in patients with advanced NSCLC, but with mild toxicity. It seems suitable for patients with advanced NSCLC as a first-line treatment.

Oncology (Hunting) 2000 Jul;14(7 Suppl 4):15-9

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Gemcitabine/cisplatin as induction therapy for stage IIIA N2 non-small-cell lung cancer.

Scagliotti GV

Department of Clinical and Biological Sciences, University of Torino, S. Luigi Gonzaga Hospital, Italy. scagliotti@ihnet.it

[Medline record in process]

Because the majority of patients with stage IIIA N2 non-small-cell lung cancer (NSCLC) ultimately die of distant metastases, recent efforts to improve their intermediate- and long-term survival have focused on neoadjuvant chemotherapy (with or without radiotherapy) as an induction regimen followed by surgical resection. Over the last 15 years, more than 25 phase II trials and two small randomized phase III trials were terminated early because interim analyses confirmed the feasibility of the neoadjuvant approach and suggested a twofold increase in overall survival time compared to surgery alone. The gemcitabine (Gemzar)/cisplatin (Platinol) regimen proved effective in unresectable locally advanced and metastatic NSCLC. Consequently, it is logical to investigate the activity of this combination in locally advanced NSCLC. Preliminary results of five phase II trials have reported an average response rate > 60% in a mixed study population (IIIA and IIIB). Treatment is well tolerated. In studies using the 4-week schedule, the gemcitabine dose was frequently omitted on day 15, mainly due to thrombocytopenia. In January 2000, a randomized clinical trial (Chemotherapy for Early Stages Trial [ChEST]) was initiated in Italy to compare the efficacy of surgery alone vs surgery plus preoperative gemcitabine/cisplatin in early-stage disease (T2-3 N0, T1-2 N1, T3 N1) with the primary end point being progression-free survival.

*** POSTED ON SEPTEMBER 4, 2000 ***