Phase II trial of carboplatin plus oral etoposide for elderly patients with small-cell lung cancer.

A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin''s carboplatin dosing formula with 14-day oral etoposide in 38 elderly patients with small-cell lung cancer (SCLC). The overall response rate was 81%. Median survival times were 15.1 months for 16 limited-disease (LD) and 8.6 months for 22 extensive-disease (ED) patients. Myelosuppression was the principal side-effect. This regimen is an active regimen in the treatment of elderly SCLC patients.     

A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer.

BACKGROUND: Superiority of irinotecan/cisplatin over etoposide/cisplatin was suggested in small-cell lung cancer (SCLC). This trial investigated irinotecan/carboplatin (IP) versus etoposide/carboplatin (EP). PATIENTS AND METHODS: The interim analysis at the phase II/phase III transition point of the multicenter trial is reported. Extensive disease SCLC patients were randomized to receive carboplatin AUC 5 mg x min/ml either in combination with 50 mg/m2 of irinotecan on days 1, 8 and 15 (IP) or with etoposide 140 mg/m2 days 1-3 (EP). The primary end point was response rate and the secondary end points were toxicity and progression-free survival. RESULTS: Seventy patients were randomized. Significant differences in grade 3 and 4 thrombopenia (17% IP versus 48% EP, P = 0.01) and neutropenia (26% IP versus 51% PE, P < 0.01) were found. Grade 3 and 4 diarrhea was more frequent with IP (18%) than with EP (6%) (P = 0.133). Response rates were 67% and 59% (P = 0.24) in the IP versus EP arm, respectively. Median progression-free survival (PFS) was 9 months (95% CI 7.1-10.9) in the IP arm and 6 months (95% CI 4.1-7.9) in the EP arm (P = 0.03). CONCLUSIONS: IP is active, less toxic and appears to improve PFS. Based on the phase II results the trial has been extended to phase III to assess the impact on overall survival.     

Phase II study of carboplatin and 1-h intravenous etoposide and paclitaxel in a novel sequence as first-line treatment of patients with small-cell lung cancer

PURPOSE: To evaluate the efficacy and tolerability of paclitaxel, carboplatin and etoposide when administered in combination to previously-untreated small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Patients (n=95) with limited-stage disease (LSD; n=45) or extensive-stage disease (ESD; n=50) from 14 Spanish hospitals were entered into the study. Etoposide was administered 80 mg/m(2)/day intravenous (i.v.) on days 1, 2 and 3, paclitaxel 175 mg/m(2) i.v. on day 3 and carboplatin area-under-the-concentration-time-curve=6; i.v. on day 3, of a 3-week cycle, and repeated for up to 6 cycles. RESULTS: The overall response (OR) rate was 74% (n=70; 32 complete, 38 partial). Although the OR in LSD and ESD patients was similar (73 vs 74%, respectively), the percentage complete response was significantly higher among the former (49 vs 20%). The main toxicities were grade 3-4 neutropenia and febrile neutropenia (62 and 18%, respectively) and there were 3 toxic deaths. Other toxicities were rare or easily manageable. Disease-free survival and overall survival rates at 1 year were 53 and 70% in LSD and 18 and 39% in ESD patients, respectively. CONCLUSION: The results indicate that the combination of paclitaxel, etoposide and carboplatin has an anti-tumour activity in SCLC that is comparable to other combination regimens, and is well tolerated.     

Phase II trial of the combination of carboplatin and irinotecan in elderly patients with small-cell lung cancer

Aim

The aim of the present phase II study was to assess the antitumour activity and safety of the combination of irinotecan and carboplatin in elderly patients with small-cell lung cancer (SCLC).

Material and methods

Patients with previously untreated SCLC were eligible if they had a performance status of 0-2, were 70 years or older, and had adequate organ function. Patients were treated with carboplatin at an area under the plasma concentration versus time curve of 5 min/ml on day 1 and with irinotecan at 50 mg/m² on days 1 and 8 every 3 weeks.

Results

Thirty patients (26 men and 4 women; median age, 76 years; age range, 70-86 years) were enrolled. Eight patients had limited disease (LD) and 22 patients had extensive disease (ED). The overall response rate was 83.3% (95% confidence interval: 65.3-94.4%). Response rates did not differ significantly between patients with LD (87.5%) and those with ED (81.8%; p = 0.71). The median survival time was 14 months overall and was significantly longer in patients with LD (26 months) than in patients with ED (11 months; p = 0.025). The median progression free survival time was 6 months overall and was significantly longer in patients with LD (12 months) than in patients with ED (6 months; p = 0.016). Grade 3-4 toxicities included neutropenia in 83% of patients, thrombocytopenia in 47%, anaemia in 60%, infection in 23%, and diarrhoea in 20%. There were no treatment-related deaths.

Conclusions

This chemotherapy is safe and effective for elderly patients with SCLC.     

Phase I/II trial of gemcitabine plus cisplatin and etoposide in patients with small-cell lung cancer

OBJECTIVE: The objectives of this phase I/II study were to define the maximum tolerated dose (MTD), safety, and activity of cisplatin, etoposide, and gemcitabine (PEG) in the treatment of previously untreated patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Chemonaive patients received fixed doses of gemcitabine (1000 mg/m(2) on days 1 and 8) and cisplatin (70 mg/m(2) on day 2) and escalating doses of etoposide (starting dose of 50 mg/m(2) on days 3, 4, and 5) every 3 weeks. No prophylactic granulocyte colony-stimulating factors were used. RESULTS: From September 1998 to April 2000, 56 patients with limited- or extensive-stage SCLC were enrolled and received a total of 235 cycles. Two different etoposide doses were tested in eight patients. At the second level (75 mg/m(2)), two out of two patients experienced dose-limiting toxicities (neutropenia and thrombocytopenia) and no further dose-escalation was attempted, thus an etoposide dose of 50 mg/m(2) was defined as the MTD. In the subsequent phase II evaluation, 48 additional patients were enrolled, for a total of 54 patients treated at the MTD. Grade 3/4 neutropenia and thrombocytopenia occurred in 66.7 and 53.7% of patients, respectively. Non-hematologic toxicity was mild, with grade 3 diarrhea and fatigue as the main side effects. Two patients died of neutropenic sepsis (one at 75 mg/m(2) and the other at 50 mg/m(2) etoposide). Ten complete and 29 partial responses were reported, for an overall response rate of 72.2% (95% confidence interval, 56.6-85.0%). The median duration of response and median survival were 8.0 and 10 months, respectively, with a 1-year survival probability of 37.5%. CONCLUSIONS: The combination of PEG is feasible and well tolerated as front-line chemotherapy in SCLC. A randomized comparison of this triplet is underway.     

Irinotecan plus carboplatin in patients with extensive-disease small-cell lung cancer

This study was designed to evaluate the efficacy and safety of irinotecan in combination with carboplatin in previously untreated, extensive-disease small-cell lung cancer (ED-SCLC). Patients with histologically or cytologically confirmed ED-SCLC received irinotecan (60 mg/m² on days 1, 8, and 15) plus carboplatin (AUC 5 on day 1) every 4 weeks. Treatment was repeated until disease progression, unacceptable toxicity, or up to 6 cycles. Forty-four patients were enrolled. In an intent-to-treat analysis, the overall response rate (RR) was 75% (8 complete responses and 25 partial responses). The median progression-free (PFS) and overall survival (OS) were 5.6 and 8.7 months, respectively. The principle toxicities were neutropenia and diarrhea. Grade 3–4 neutropenia occurred in 30% of the patients and 7% of patients presented with febrile neutropenia. Grade 3–4 diarrhea occurred in 21% of the patients. A subgroup consisting of patients ≥65 years of age had outcomes similar to the younger group <65 years of age. The objective RR was 72% in the patients <65 years of age and 77% in the patients ≥65 years of age (P = .738). The median PFS and OS (<65 years vs. ≥65 years) were 5.3 vs. 5.6 months (P = .835) and 9.0 vs. 8.7 months (P = .648), respectively. The combination of irinotecan and carboplatin is active and tolerable in patients with ED-SCLC. This regimen could be considered as a treatment option for patients of advanced age.     

Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer

To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial. Eligibility criteria were: chemotherapy-naïve, small-cell lung cancer (SCLC), good performance status (PS: 0–2), age⩽75 years, and adequate organ function. The patients'' characteristics were: male/female=56/5; PS 0/1/2=19/38/4; median age (range)=68 years(51–75 years); limited disease (LD)/extensive disease (ED)=27/34. The patients received irinotecan (50 mg m⁻²) on days 1, 8, and 15, and carboplatin (AUC 5, Chatelut formula) on day 1 every 4 weeks. In total, 61 patients were eligible and all were evaluated. In all, 31 patients were treated with four or more courses of chemotherapy. Of the patients, 17 showed a complete response (CR), 34 showed a partial response (PR), nine had stable disease (SD), and one had progressive disease (PD). The overall response rate was 84% (95% confidence interval (CI), 72–91%; LD 89%, ED 79%) and the CR rate was 28% (95%CI, 17–41%; LD 37%, ED 21%). The median time to tumour progression was 6.1 (LD 6.4, ED 5.4) months. The medial survival time was 15.0 (LD 20.0, ED 9.7) months, and the 2-year and 5-year survival rates were 31.1% (LD 48.1%, ED 17.7%) and 9.5% (LD 11.1%, ED 5.9%), respectively. Grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, anaemia, and diarrhoea occurred in 33, 74, 41, 39, and 13% of cases, respectively. In conclusion, the combination of irinotecan and carboplatin is an active and well-tolerated regimen in cases of SCLC.     

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

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 >/=70 and performance status 0-2, or age <70 and PS 3. The CE arm received carboplatin area under the curve of five intravenously (IV) on day 1 and etoposide 80 mg m(-2) IV on days 1-3. The SPE arm received cisplatin 25 mg m(-2) IV on days 1-3 and etoposide 80 mg m(-2) 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=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.     

Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: A phase II study

Background:Although the average age of lung cancer patients isincreasing, many elderly patients remain undertreated, mainly because of thefear of higher treatment toxicity in this category of patients. We conducteda study to evaluate the efficacy and tolerability of a combination therapywith carboplatin (C) and etoposide phosphate (EP) in elderly patients withSmall-Cell Lung Cancer (SCLC).Patients and methods:Previously untreated patients older than 70years with stage IIIB/IV SCLC received a combination of EP (100mg/m² D1, D2, D3) and C (D1, dose calculated according to theCalvert formula). Response rate, survival and toxicity were assessed.Results:Thirty-eight patients (mean age 76 years, range70–88 years) received a total of 162 cycles. Eighteen patients(47%) received the six scheduled cycles. Thirty patients were evaluablefor efficacy (2 CR and 20 PR). The median survival was 237 days and theone-year probability of survival was 26%. The most common adverseeffect was transient grade 3 or 4 neutropenia, observed during 57% ofevaluable cycles, while five episodes of febrile neutropenia also occurred,with one fatal (bactaeriemia). It is noteworthy that no renal or livertoxicity was observed, and no mucitis was noted. Unfortunately, a relativelyhigh proportion of patients died shortly after the start of the study.Although most deaths seemed unrelated to the treatment, the possibility of itsexacerbatory effect on comorbidities, especially cardiovascular, cannot beexcluded.Conclusion:The two-drug regimen of carboplatin and etoposidephosphate is feasible in most elderly patients with an acceptable toxicity,and the overall results suggest that patients even older than 70 years maybenefit from full treatment. Therefore, consideration should be given tooffering active treatment to most patients with SCLC, regardless of age butwith special attention paid to comorbidities.     

Phase II study of ifosfamide and etoposide chemotherapy for extensive-disease small-cell lung cancer

We conducted a phase II study of ifosfamide and etoposide chemotherapy in patients with untreated extensive-disease small-cell lung cancer to assess response and toxicity. Between January 1994 and December 1995, 16 patients were treated. Ifosfamide and etoposide doses were ifosfamide 2 g/m2, with mesna, i.v. infusion over 30 minutes on days 1-3 and etoposide 80 mg/m2 i.v. over 120 minutes on days 1-3 every 4 weeks for up to six cycles. All patients were evaluable for toxicity profile and treatment response. As expected, the major toxicity was myelosuppression. With one exception, grade 3 or 4 leukopenia occurred in all patients during treatment, and 48.7% of the total courses had grade 3 or 4 leukopenia. Nine of 16 patients (56.3%) experienced episodes of febrile neutropenia. One toxic death due to febrile neutropenia with sepsis was documented. Toxicities other than leukopenia were few and mild in severity. After two cycles of treatment, the overall response rate was 81.3% (95% confidence interval 62.2-100) in this study. The median duration of response was 8 months and median survival was 11 months. In conclusion, ifosfamide and etoposide is an active combination regimen with acceptable toxicity profile in Chinese patients with extensive-disease small-cell lung cancer.      

Phase II study of carboplatin in patients with nonresected lung cancer

Summary A multicenter phase II trial of carboplatin, a new platinum analog of cisplatin, was carried out in bronchogenic carcinoma at 17 institutions throughout Japan. Of 139 patients enrolled in this trial, 10 were excluded from analysis as inevaluable and the remaining 129 were judged to be evaluable for response and toxic effects by the Extramural Review Committee. Patients were treated i. v. with either 300 or 400 mg/m² carboplatin every 4 weeks. Responses and toxic effects were assessed at both dose levels. The overall response rate was 17.8% (23/129), with response rates of 28.4% (19/67) for small-cell disease, 7.1% (2/28) for squamous-cell carcinoma, and 6.9% (2/29) for adenocarcinoma. The most frequent toxic effects were thrombocytopenia and leukopenia, with a platelet count of <7 × 10⁴ μl recorded in 60 patients (46.5%) and a WBC count of <3,000/μl recorded in 60 cases (46.5%). Vormiting occurred in 28 patients (21.7%). Renal, aural, and neurotoxicities were not seen. Hydration was not required. Carboplatin was demonstrated to be active against lung cancer, especially against small-cell lung cancer. Participating members: Kiyoji Kimura, Nagoya Memorial Hospital; Akira Suzuki, Sapporo Medical College; Kiyosi Konno, The Research Institute for Tuberculosis and Cancer, Tohoku University; Kotaro Oizumi², The Research Institute for Tuberculosis and Cancer, Tohoku University; Koich Hasegawa, Tsuboi Hospital; Takeshi Honma, Saitama Cancer Center; Toshiro Ogata, National Defence Medical College School of Medicine; Yutaka Nisiwaki², Matsudo National Hospital: Takayuki Kuriyama, Institute of Pulmonary Cancer Research. School of Medicine, University of Chiba; Hisanobu Niitani¹, Nippon Medical School; Kenji Eguchi³, National Cancer Center; Yasunobu Kuraishi, The Jikei University School of Medicine; Makoto Ogawa, Japanese Foundation for Cancer Research; Kazuo Ohta, Aichi Cancer Center: Shunsaku Oshima², Chest Disease Research Institute, Kyoto University; Masahiro Fukuoka², Osaka Prefectural Habikino Hospital; Kiyoyuki Furuse², Kinki National Center Hospital; Ikuro Kimura, Okayama University medical School; Taisuke Onoshi², Okayama University medical School; Mitsuo Ohta, National Kyushu Cancer Center; Nobuyuki Hara², National Kyushu Cancer Center Chairman for lung cancer Reviewer Extramural reviewer Offprint requests to: H. Niitani, Department of Clinical Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113, Japan     

Phase II trial of combination chemotherapy with cisplatin, carboplatin and etoposide in stage IIIB and IV small-cell lung cancer

Purpose: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. Methods: Previously untreated patients with small-cell lung cancer, with measurable disease, aged ≤ 72 years, performance status ≤ 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m² cisplatin on day 1, 100 mg/m² carboplatin on days 2, 3 and 8, and 50 mg/m² etoposide on days 1, 2, 3 and 8. Results: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively. Conclusions: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer. Received: 21 May 1997 / Accepted: 11 September 1997     

Phase II study of irinotecan plus cisplatin with concurrent radiotherapy for the patients with limited-disease small-cell lung cancer

BACKGROUND: A recently conducted randomized, phase III study that compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin for the patients with extensive disease SCLC revealed a superior median survival rate and a superior 2-year survival rate for the IP combination therapy. Yet there have been few such reports on the patients suffering with limited disease SCLC (LD-SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of administering IP with concurrent radiotherapy for the patients with LD-SCLC. PATIENTS AND METHODS: Twenty chemotherapy-na?ve patients with LD-SCLC were enrolled in our study. The patients were treated with 40 mg/m(2) irinotecan on days 1, 8 and 15 and with 60 mg/m(2) cisplatin on day 1 every 4 weeks until a maximum of six cycles was delivered. Once-daily radiotherapy included the administration of 50.4 Gy in 28 fractions. After completion of the radiation therapy, the dose of irinotecan was increased to 60 mg/m(2). RESULTS: The response rate was 85% (CR: 6; partial response, PR: 11). The median survival was 20.0 months (95% CI: 15.6-24.4 months) with 1-year and 2-year overall survival rates of 85 and 35%, respectively. The median progression free survival (PFS) was 12 months (95% CI: 6.2-18.1 months) with a 1-year PFS of 36%. The major hematologic toxicities of this regimen were neutropenia (60%), leukopenia (55%), anemia (20%) and thrombocytopenia (10%). The non-hematologic toxicities were nausea/vomiting (55%), diarrhea (35%) and dysphagia (15%). CONCLUSIONS: Our data show that IP with concurrent radiotherapy is an effective and tolerable regimen for the treatment of LD-SCLC and these findings warrant further investigation.     

CPE和CE方案治疗小细胞肺癌的疗效比较

目的　评价CPE(卡铂、顺铂、足叶乙甙)和CE(卡铂、足叶乙甙)方案治疗小细胞肺癌(SCLC)的疗效和毒性。方法　应用CPE和CE方案治疗32例SCLC患者,每组16例,CPE组和CE组中的复治病例分别为10例和7例。结果　CPE组和CE组的有效率分别为81.3%(13/16)和87.5%(14/16)(P>0.05)。CPE组与CE组中的复治病例有效率分别为60%(6/10)和42.9%(3/7)(P<0.05)。CPE组与CE组的骨髓抑制率分别为71.9%和93.8%(P<0.05)。两组间其它毒性反应差异无显著性(P>0.05)。结论　CPE方案治疗SCLC的疗效与CE方案相近,但CPE的骨髓抑制明显较CE轻;CPE对复治病例的疗效优于CE。     

Phase II study of irinotecan plus cisplatin induction followed by concurrent twice-daily thoracic irradiation with etoposide plus cisplatin chemotherapy for limited-disease small-cell lung cancer.

PURPOSE: Irinotecan plus cisplatin (IP) chemotherapy demonstrated a promising outcome with a high complete response (CR) rate in chemotherapy-na?ve patients with extensive small-cell lung cancer (SCLC). We evaluated the efficacy of induction IP chemotherapy followed by concurrent etoposide plus cisplatin (EP) chemotherapy with twice-daily thoracic radiotherapy (TDTRT) in limited-disease SCLC (LD-SCLC). PATIENTS AND METHODS: Between November 2001 and May 2003, 35 chemotherapy-na?ve patients with LD-SCLC were enrolled. Thirty-three patients (94%) were male, and 29 (83%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median age was 63 years. Treatment consisted of two 21-day cycles of cisplatin 40 mg/m2 and irinotecan 80 mg/m2 intravenously (i.v.) on days 1 and 8 followed by two 21-day cycles of cisplatin 60 mg/m2 i.v. on days 43 and 64, and etoposide 100 mg/m2 i.v. on days 43 to 45 and 64 to 66, with concurrent TDTRT of total 45 Gy beginning on day 43. RESULTS: All 35 patients were assessable for response. The objective response rate was 97% (CR, 3; partial response [PR], 31) after induction chemotherapy and 100% (CR, 15; PR, 20) after concurrent chemoradiotherapy (CCRT). After a median follow-up of 26.5 months, the median survival was 25.0 months (95% CI, 19.0 to 30.9) with 1- and 2-year overall survival rates of 85.7% and 53.9%, respectively. Median progression-free survival (PFS) was 12.9 months with a 1- and 2-year PFS of 58.5% and 36.1%, respectively. The most common toxicities were grade 3 or 4 neutropenia in 68% of patients during induction chemotherapy and 100% during CCRT. Febrile neutropenia occurred in 20% of patients during induction chemotherapy and 60% during CCRT. CONCLUSION: IP induction chemotherapy followed by concurrent TDTRT with EP chemotherapy showed a promising activity with favorable 1- and 2-year survival rates. Based on the favorable outcome in this trial, this regimen should be evaluated in a large phase III trial.     

Phase II study of cisplatin/etoposide and endostar for extensive-stage small-cell lung cancer

Purpose  

To investigate the efficacy and safety of endostar, a novel recombinant human endostatin, plus cisplatin, and etoposide in patients with extensive-stage small-cell lung cancer (ED-SCLC).     

Phase III study of cyclophosphamide, doxorubicin, and etoposide compared with carboplatin and paclitaxel in patients with extensive disease small-cell lung cancer

The progression-free survival (PFS) of cyclophosphamide/doxorubicin/etoposide (CDE) and carboplatin/paclitaxel (CP) was compared in chemonaive patients with extensive disease small-cell lung cancer (ED-SCLC). A total of 203 patients were randomised to three-weekly CDE (n=102) or CP (n=101) for five cycles. Tumour response rates in CDE and CP were 60% and 61%. PFS of CP was 5.2 months, PFS of CDE 4.9 months (p=0.60). The major difference in toxicity between CDE and CP was grade 4 leukocytopaenia in 64% and 9% of the patients (p<0.0001), leading to febrile neutropaenia in 30% and 4% of the patients (p<0.0001), respectively. This was the reason for differences in the total number of hospital admissions (63 for CDE and 40 for CP, p=0.0025). This study failed to demonstrate any benefit in PFS with CP compared with CDE. CP was associated with significantly less haematological toxicity, leading to 37% less hospital admissions for febrile neutropaenia.     

Pharmacokinetic analysis of combination chemotherapy with carboplatin and etoposide in small-cell lung cancer patients undergoing hemodialysis.

BACKGROUND: The aim of this study was to use pharmacokinetic analysis to investigate the efficacy and toxicity of combined chemotherapy with carboplatin (CBDCA) and etoposide (ETP) in small-cell lung cancer (SCLC) patients with chronic renal failure undergoing hemodialysis (HD). PATIENTS AND METHODS: Three SCLC patients with chronic renal failure undergoing HD were treated with CBDCA (300 mg/m(2)) on day 1 and ETP (50 mg/m(2)) on days 1 and 3, followed by HD 1 h after completing the administration of anticancer agents on each day. The pharmacokinetic analysis of CBDCA and ETP was planned for at least the first two courses of the chemotherapy in each patient. RESULTS: Two complete responses and one partial response were achieved in the three patients. Two patients experienced grade 3/4 neutropenia and required blood transfusion due to thrombocytopenia and anemia. Non-hematological toxicities were moderate. The pharmacokinetic analysis revealed that the platinum and the ETP concentrations in the plasma were similar to those in patients with normal renal function during the first 24 h, while the platinum still remained in the plasma for over 90 h. CONCLUSIONS: Chemotherapy with CBDCA (300 mg/m(2) on day 1) and ETP (50 mg/m(2) on day 1, 3) as used in the present study may be a suitable regimen for SCLC patients undergoing HD, although careful attention should be given to hematological toxicities.     

Phase I study of G3139, a bcl-2 antisense oligonucleotide, combined with carboplatin and etoposide in patients with small-cell lung cancer.

PURPOSE: Bcl-2 is expressed in the majority of cases of small cell lung cancer (SCLC) and may contribute to chemotherapeutic resistance. Bcl-2 suppression by G3139 (oblimersen sodium), a phosphorothioate oligonucleotide complementary to the bcl-2 mRNA, has the potential to enhance the antitumor efficacy of standard cytotoxic chemotherapy. A dose-finding study was performed evaluating the combination of G3139, carboplatin, and etoposide in patients with previously untreated extensive stage SCLC. PATIENTS AND METHODS: Sixteen patients were treated in three consecutive cohorts. Cohort 1 (n=5) received G3139 5 mg/kg/d on days 1 to 8 of a 21 day cycle, with carboplatin area under the curve (AUC)=6 on day 6, and etoposide 80 mg/m2/d on days 6 to 8. In cohort 2 (n=4), carboplatin dose was reduced to AUC=5. In cohort 3 (n=7), G3139 dose was escalated to 7 mg/kg/d. G3139 plasma concentrations and Bcl-2 protein levels in peripheral blood mononuclear cells were evaluated. RESULTS: Two of three assessable patients in cohort 1 experienced cycle 1 dose-limiting toxicity (grade 4 neutropenia). No cycle 1 dose-limited toxicity was observed in cohorts 2 or 3. Of 14 patients assessable for response, partial response was documented in 12 patients (86%), and stable disease in two. Median time to progression was 5.9 months. Carboplatin and etoposide administration did not appear to alter G3139 pharmacokinetics. No evidence of Bcl-2 suppression in peripheral blood mononuclear cells was observed. CONCLUSION: The combination of G3139, carboplatin, and etoposide is well tolerated and results in an encouraging response rate and time to progression in patients with extensive stage SCLC.