Phase II Study of Area Under the Plasma-Concentration-Versus-Time Curve–Based Carboplatin Plus Standard-Dose Intravenous Etoposide in Elderly Patients With Small-Cell Lung Cancer

Okamoto, Hiroaki; Watanabe, Kenji; Nishiwaki, Yutaka; Mori, Kiyoshi; Kurita, Y; Hayashi, Izumi; Masutani, Masayuki; Nakata, Kohei; Tsuchiya, Satoshi; Isobe, Hiroshi; Saijo, Nagahiro

doi:10.1200/jco.1999.17.11.3540

Cited by 87 publications

(53 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The CE regimen, which has acceptable toxicities and reproducible efficacy, has been used in elderly or poor-risk patients with SCLC worldwide, although there have been substantial differences in toxicities and efficacy between the reported phase II trials. Four trials demonstrated both favourable toxicities and efficacy (Carney, 1995;Evans et al, 1995;Matsui et al, 1998;Okamoto et al, 1999) and three showed somewhat disappointing results because of suboptimal doses of oral etoposide (Larive et al, 2002), greater inclusion of patients with poor prognostic factors (Samantas et al, 1999), and deterioration of comorbidities as a result of chemotherapy (Quoix et al, 2001). No phase III trial evaluating the role of the CE regimen in this population has been reported until now.…”

Section: Discussionmentioning

confidence: 99%

“…Cycles were repeated every 3 -4 weeks for up to four courses. In our previous phase II study using the CE regimen for elderly patients with SCLC, carboplatin AUC of 5 on day 1 and etoposide 100 mg m À2 on days 1, 2, and 3 were administered every 4 weeks (Okamoto et al, 1999). However, because grade 3 or 4 neutropenia occurred in 91% of the patients, in the current phase III trial we decided to reduce the etoposide dosage to 80 mg m À2 on days 1, 2, and 3, and repeat the cycle every 3 -4 weeks instead of every 4 weeks.…”

Section: Treatment Protocolmentioning

confidence: 99%

“…However, since many investigators have arbitrarily excluded elderly patients from clinical trials, no standard chemotherapeutic regimen has been established for elderly patients with SCLC. The Japan Clinical Oncology Group (JCOG) has reported that carboplatin plus etoposide (CE) is an active and less toxic regimen in elderly patients with SCLC (Okamoto et al, 1999). However, other clinical trials have indicated that the combination chemotherapy of reduced (Souhami et al, 1997) or split doses of cisplatin plus etoposide (SPE) Westeel et al, 1998) can be safely and effectively administered in elderly or poor-risk patients with SCLC.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702

et al. 2007

View full text Add to dashboard Cite

We compared the efficacy and the safety of a carboplatin plus etoposide regimen (CE) vs split doses of cisplatin plus etoposide (SPE) in elderly or poor-risk patients with extensive disease small-cell lung cancer (ED-SCLC). Eligibility criteria included: untreated ED-SCLC; age X70 and performance status 0 -2, or age o70 and PS 3. The CE arm received carboplatin area under the curve of five intravenously (IV) on day 1 and etoposide 80 mg m À2 IV on days 1 -3. The SPE arm received cisplatin 25 mg m À2 IV on days 1 -3 and etoposide 80 mg m À2 IV on days 1 -3. Both regimens were given with granulocyte colony-stimulating factor support in a 21 -28 day cycle for four courses. A total of 220 patients were randomised. Median age was 74 years and 74% had a PS of 0 or 1. Major grade 3 -4 toxicities were (%CE/%SPE): leucopenia 54/51, neutropenia 95/90, thrombocytopenia 56/16, infection 7/6. There was no significant difference (CE/SPE) in the response rate (73/73%) and overall survival (median 10.6/9.9 mo; P ¼ 0.54). Palliation scores were very similar between the arms. Although the SPE regimen is still considered to be the standard treatment in elderly or poor-risk patients with ED-SCLC, the CE regimen can be an alternative for this population considering the risk -benefit balance.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Treatment Protocolmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702

et al. 2007

View full text Add to dashboard Cite

show abstract

“…A Japanese phase II trial [76] conducted in 1995-1996, also supports the supposition that a reasonably high initial dose level is important for the outcome. Thus, 36 patients, aged 73 yrs (70-80 yrs), received up to 4 cycles of carboplatin (AUC 5) plus etoposide 100 mg?m -2 i.v.…”

Section: Elderly Patientsmentioning

confidence: 73%

Chemotherapy in small cell lung cancer

Østerlind¹

2001

Eur Respir J

View full text Add to dashboard Cite

Chemotherapy is the backbone in the treatment of small cell lung cancer (SCLC) and radiotherapy is an important adjunct in limited stage disease. The role of chest irradiation is now documented in three meta-analysis, based on the same body of data. Trials on timing, scheduling and fractionation could have followed a more stringent development line but altogether, the highest efficacy seems to be obtained with early, concurrent twice-daily chest irradiation. Patients in complete remission should have prophylactic cranial irradiation, which reduces the risk of brain metastases and of death from SCLC.Four series of chemotherapy seem to be sufficient in limited-stage disease while six is recommended in extensive disease. The combination of etoposide plus cis- or carboplatin is appropriate in both stages and addition of other agents has no clinically important impact on the survival. Use of haematological growth factors such as granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) may enable higher doses or more frequent dosage. Three randomized trials on GM-CSF showed a negative outcome while G-CSF support may result in better survival rates, but a more cost-efficient policy must be found. High-dose chemotherapy plus haematological stem-cell support is still under investigation but disappointing long-term survival rates means there is not much optimism for this strategy.New strategies in general are requested in the treatment of extensive-stage disease and of elderly patients. Phase II trials suggest that good-risk patients with extensive disease should be treated aggressively, intermediate-risk patients more gently, and palliation must be the primary aim in the treatment of poor-risk patients. In elderly patients impressive survival rates are obtained with 3–4 series of chemotherapy and radiation delivered in 5–10 fractions.A number of new agents are active but more trials are required before each has found a place, if any, in the treatment of small cell lung cancer. To conclude, the randomized trial is still an important instrument in clinical oncology, and trials in small cell lung cancer must be large, which is why the cooperation of organizations and multicentres is urgent.

show abstract

“…The combination ofAUCbased carboplatin and a standard dose of intravenous etoposide is an active and relatively non-toxic regimen. In a study using this regimen, the response rate was75%,the mediansurvival time was 10.8 months, and the 1-and 2-year survival rates were 47.2% and 15.4% (3). As a result of carboplatin and etoposide therapy, the present patient achieved complete remission and a PS score of 0.…”

Section: Five-year Survivor Of Small Cell Lung Cancer Portional Hazarmentioning

confidence: 74%

Response to Combined Modality Treatment in a Five-year Survivor of Extensive Small Cell Lung Cancer with Severe Complications.

Okamoto

Nagatomo

et al. 2000

Intern. Med.

Self Cite

View full text Add to dashboard Cite

Wepresent a rare case of a five-year survivor of small cell lung cancer with severe complications whoresponded to combined modality treatment. Prior to initial chemotherapy, he experienced severe complications including sepsis, pneumonia, ileus, and a performance status of 4. He was treated with an ileus tube and IVH, and was managed by mechanical ventilation for four days. After his general condition improved, he received combination chemotherapy of carboplatin, with the target area under the plasma concentration versus the time curve (AUC)of 5 mgà"min/ml day 1, and etoposide (80 mg/m2) on days 1, 2, 3 for four courses, and complete remission (CR) was obtained. Six months later, systemic relapse occurred, but he achieved complete remission again with nine courses of CODE (cisplatin, vincristine, adriamycin, and etoposide) chemotherapy and sequential chest radiotherapy. Five years after the initial chemotherapy, the patient is alive and disease free.

show abstract

Phase II Study of Area Under the Plasma-Concentration-Versus-Time Curve–Based Carboplatin Plus Standard-Dose Intravenous Etoposide in Elderly Patients With Small-Cell Lung Cancer

Abstract: This carboplatin/etoposide combination chemotherapy is an active and relatively nontoxic regimen in elderly patients with SCLC, which suggests that the combination may be suitable for randomized controlled trials.

Cited by 87 publications

References 20 publications

Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702

Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702

Chemotherapy in small cell lung cancer

Response to Combined Modality Treatment in a Five-year Survivor of Extensive Small Cell Lung Cancer with Severe Complications.

Contact Info

Product

Resources

About