A multicenter phase II study of combined chemotherapy with docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer (KDOG 0601)

Purpose

We conducted a phase II study to evaluate the efficacy and safety of a triplet regimen of docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer.

Methods

Docetaxel (40?mg/m²) and cisplatin (70 or 60?mg/m²) were given on day 1 of a 28-day cycle. S-1 (40?mg/m²) was given twice daily on days 1?C14. Treatment with this regimen was continued for a maximum of 6 cycles. Subsequently, patients with no disease progression received a combination of docetaxel and S-1.

Results

Fifty-nine patients were enrolled. The median number of administered cycles was 8 (range, 1?C25). Because some patients had serious myelosuppression and renal dysfunction with 70?mg/m² of cisplatin, dose of cisplatin was reduced to 60?mg/m² after 19 patients had been treated. Common severe toxic effects of grade 3 or 4 were leukocytopenia (44%), neutropenia (72%), anemia (15%), and febrile neutropenia (14%). The overall response rate of this group was 81% (95% confidence interval (CI), 71?C91%). The median overall survival and progression-free survival were 18.5 (95% CI, 15.6?C21.5) and 8.7 (95% CI, 6.7?C10.7) months, respectively.

Conclusions

Triplet of docetaxel, cisplatin, and S-1 is a well-tolerated and highly active regimen for advanced or recurrent gastric cancer. A 60?mg/m² of cisplatin is as effective as 70?mg/m² of cisplatin.     

Second-line chemotherapy with irinotecan plus cisplatin after the failure of S-1 monotherapy for advanced gastric cancer

Background

For advanced gastric cancer (AGC), second-line chemotherapy after the failure of S-1 has not yet been established. The present study aimed to retrospectively evaluate the efficacy and safety of irinotecan plus cisplatin (IP) therapy after the failure of S-1 in patients with AGC.

Methods

The subjects included 87 patients with AGC who received IP therapy as second-line chemotherapy. Irinotecan (70 mg/m²) was administered by intravenous infusion followed by an intravenous infusion of cisplatin (80 mg/m²) on day 1. On day 15, irinotecan (70 mg/m²) alone was administered. The treatment was repeated every 4 weeks until disease progression, patient refusal, or severe adverse events.

Results

The median patient age was 62 years (range, 39–75 years), and the median number of treatment cycles was 3 (range, 1–9). Out of the 87 patients, 70 were assessable for clinical response. There were 2 complete responses and 18 partial responses. The overall response rate was 28.6% (95% confidence interval [CI], 18.4%–40.6%) and the disease control ratio was 70.0%. The median time to progression and median survival time from the first day of IP therapy were 4.3 months and 9.4 months, respectively. The 1-year survival rate was 34.6%. Severe (grade 3/4) leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 34%, 40%, 28%, and 8% of patients, respectively. Grade 3/4 nonhematologic toxicities included anorexia (17%), febrile neutropenia (10%), diarrhea (6%), fatigue (5%), nausea (2%), and elevated creatinine (1%).

Conclusions

The combination of irinotecan plus cisplatin as second-line chemotherapy for AGC appears to be an effective and feasible treatment option after S-1 failure.     

Multicenter phase II study of weekly paclitaxel plus S-1 combination chemotherapy in patients with advanced gastric cancer

Background

A multicenter phase II study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus S-1 in patients with advanced gastric cancer.

Methods

Patients with previously untreated metastatic or recurrent gastric cancer received intravenous paclitaxel 50 mg/m² on days 1, 8, and 15, plus oral S-1 40 mg/m² b.i.d. on days 1 to 14 followed by 2 weeks off, in a 28-day cycle.

Results

A total of 54 patients were registered. All of them had measurable disease and were determined to be eligible for the present study. Two complete responses and 23 partial responses were confirmed, giving an overall response rate of 46.3%. At a final follow up of 3 years, the median progressionfree survival and median overall survival were 6.0 and 14.3 months, respectively. Grade 3 neutropenia occurred in 14 patients, and grade 4 in 1 patient (total, 27.8%). The most serious nonhematological toxicity was diarrhea, where grade 3 occurred in 5 patients (9.3%). There were no treatmentrelated deaths.

Conclusion

A combination of weekly paclitaxel plus S-1 was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation with comparative trials is needed for confirmation.     

Phase II study of S-1 monotherapy in paclitaxel- and cisplatin-refractory gastric cancer

Purpose

S-1 is a fourth-generation oral fluoropyrimidine that was developed to mimic the effects achieved with protracted continuous infusion of 5-fluorouracil (5-FU). This phase II study evaluated the efficacy and safety of S-1 salvage chemotherapy in patients with paclitaxel- and cisplatin-refractory gastric cancer. The primary end point was progression-free survival; secondary end points were overall survival, safety, and clinical benefit.

Methods

Patients were eligible for the study if they had histologically documented gastric adenocarcinoma previously treated with paclitaxel and cisplatin, age ≥ 18 years, Eastern Clinical Oncology Group performance status ≤2, adequate organ function, and no evidence of gastrointestinal obstruction or passage disturbance. Patients were treated with a dose of S-1 based on body surface area (BSA) as follows: BSA < 1.25 m², 80 mg/day; 1.25 ≤ BSA < 1.5 m², 100 mg/day; BSA ≥ 1.5 m², 120 mg/day. The total dose was divided in two and administered twice daily for 4 weeks followed by a 2-week rest period.

Results

Of the 53 patients enrolled in this study, 49 were evaluable. A total of 190 chemotherapy cycles were administered, and the median number of cycles was 2. Five patients (9.4%) had a partial response, and 18 (34%) had stable disease. Median progression-free survival and overall survival were 4.9 and 10.4 months, respectively. Grade 3/4 hematological toxicities included neutropenia in six patients (11%) but no cases of febrile neutropenia were found. Most of the non-hematological toxicities were diarrhea, asthenia, and mucositis, but none reached grade 3 or grade 4 in severity. Improvement of pain was observed in 17 patients (32.1%).

Conclusions

S-1 monotherapy provides active and safe salvage chemotherapy for patients with advanced gastric cancer who have been previously treated with paclitaxel and cisplatin.     

Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer

Background:

A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting.

Methods:

Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m⁻² twice daily) on days 1–14 plus paclitaxel (60 mg m⁻²) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m⁻² twice daily) on days 1–21 plus cisplatin (60 mg m⁻²) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.

Results:

A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7% P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin.

Conclusion:

S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials.     

Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer

Purpose

We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer.

Methods

Patients with histologically proven, unresectable metastatic gastric adenocarcinoma, performance status (PS) 0–2, and no prior chemotherapy were eligible. Patients received oral S-1 (40 mg/m² b.i.d.) on days 1–14 and intravenous cisplatin (60 mg/m²) and docetaxel (60 mg/m²) on day 8 every 3 weeks.

Results

Thirty-four patients were enrolled between March 2005 and April 2007. Three patients were considered ineligible and did not receive the DSC therapy. Clinical characteristics were as follows: median age, 63 years (range, 44–77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well-differentiated/undifferentiated adenocarcinoma, 10/21. The objective response rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%) in 31 assessable patients. Four had stable disease (12.9%) but none had progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7 (22.6%) underwent curative surgery. The median survival time and progression-free survival were 687 days [confidence interval (95% CI), 600.0–1,138.1] and 226 days (95% CI, 182.5–379.3), respectively. Most common grade 3/4 hematologic toxicity was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved, and no toxic deaths were observed.

Conclusions

DCS combination chemotherapy is highly active against unresectable metastatic gastric cancer and can be given safely with proper management of adverse events. Further studies of this combination are warranted.     

Weekly paclitaxel for heavily treated advanced or recurrent gastric cancer refractory to fluorouracil, irinotecan, and cisplatin

Background

Although triweekly administration of paclitaxel is approved for gastric cancer in Japan, currently, the drug is often delivered with a weekly schedule because of the equivalent efficacy and lesser toxicity of this dosing schedule as compared with the triweekly administration schedule. Weekly administration of paclitaxel as second-line or first-line chemotherapy for gastric cancer has been reported to yield a response rate of about 20%. Because there has been no report of the efficacy of weekly paclitaxel in the third-line setting, this retrospective study investigated the efficacy and toxicities of weekly paclitaxel used in the third-line setting for the treatment of gastric cancer refractory to all three key drugs, fluorouracil, irinotecan, and cisplatin, used in clinical practice.

Methods

In 85 patients with advanced or recurrent histologically confirmed gastric adenocarcinoma who had failed to respond to prior chemotherapy regimens containing fluorouracil, irinotecan, and cisplatin, paclitaxel (80 mg/m²) was administered weekly, three times, for 3 weeks out of 4.

Results

The median number of courses was 3 (range, 1–38). The overall response rate was 23.2% (19/82) in the patients with measurable lesions, and ascites disappeared in 15 of 48 patients (31.3%). Progression-free survival was 105 days and the median survival time was 201 days from the initiation of paclitaxel administration. Grade 3 or 4 leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 25 (29%), 25 (29%), 37 (44%), and 3 (4%) patients. Other, nonhematological, toxicities were nausea, vomiting, anorexia, sensory neuropathy, fatigue, and febrile neutropenia.

Conclusion

Weekly paclitaxel administration shows activity against advanced gastric cancer also in the third-line setting.     

周剂量紫杉醇联合替吉奥治疗晚期胃癌(英文)

Objective:There remains no standard first-line chemotherapeutic regimen for advanced gastric cancer (AGC).The aim of this study was to evaluate the efficacy and safety of combination regimen with weekly paclitaxel and S-1 as a first-line chemotherapy for AGC. Methods:Forty-six patients with AGC were included in this study. Paclitaxel was administered weekly at a dose of 60 mg/m2 on days 1, 8 and 15, S-1 was administered orally twice daily at 80 mg/m2/day for 2 weeks. The regimen was repeated every four weeks. Results:The results showed that the overall response rate was 45.7%, with 3 patients achieved complete response and 18 patients had a partial response, the disease control rate was 76.1%. The median progress free survival was 7.2 months 95% confidence interval (CI):6.3-8.1 months and the median overall survival was 11.6 months (95% CI:10.6-12.6 months) after treatment with paclitaxel and S-1. Neutropenia occurred in 25 patients (54.3%) and grade 3/4 neutropenia was observed in 8 patients (17.4%), gastrointestinal reactions were the most common non-hematologic toxicities, while severe gastrointestinal toxicities were uncommon. Conclusion:The regimen of weekly paclitaxel and S-1 demonstrated activity and acceptable toxicity for AGC as a first-line chemotherapy.     

奥沙利铂联合替吉奥胶囊治疗晚期胃癌患者62例的临床观察(英文)

Objective:The aim of this study was to evaluate the efficacy and safety profile of DeFazio(S-1)combined with oxaliplatin against unresectable advanced or metastatic gastric cancer.Methods:Oxaliplatin was given intravenously at 130mg/m2for 2 h on d1 and S-1 was administered bid.at 80 mg/m2/day on d1–14 followed by a 7-day rest during the 3-week schedule.Results:All 62 patients were assessed for efficacy and adverse events.The response and disease control rates were 47.3%and 80.8%,respectively.The median time to progression was 7.8 months,and the median overall survival was11.6 months.The grade 3/4 adverse events were hematological toxicities,including neutropenia(11.3%),thrombocytopenia(9.7%)and gastrointestinal reactions(6.5%).Conclusion:The SOX regimen(oxaliplatin,130 mg/m2d1;S-1,80 mg/m2/day,bid.d1-14,q3w)provide a favorable efficacy and safety profile in patients with advanced gastric cancer.     

Three-week combination chemotherapy with S-1 and cisplatin as first-line treatment in patients with advanced gastric cancer: a retrospective study with 159 patients

Background

Doses and schedules of the combination of S-1 and cisplatin for the treatment of advanced gastric cancer (AGC) have not been standardized. We therefore evaluated the efficacy and feasibility of a 3-week schedule of S-1 and cisplatin in patients with AGC, as well as assessing factors prognostic of patient outcomes.

Methods

A total of 159 patients with AGC were treated with S-1 (40?mg/m² bid on days?1–14) and cisplatin (60?mg/m² IV on day?1) between January 2004 and December 2008.

Results

Median follow-up duration was 20.0?months (range, 11.4–48.5?months), during which time 129 patients (81.1%) died. Patients received a median 6 cycles of chemotherapy (range, 1–19 cycles). Among the 59 patients with measurable disease, 1 achieved a complete response (1.7%) and 24 (40.7%) had partial responses, giving an overall response rate of 42.4% (95% CI, 23.0–61.8%). The median progression-free survival (PFS) was 5.8?months (95% CI, 4.8–6.9?months), and the median overall survival (OS) was 11.3?months (95% CI, 9.6–13.0?months). Multivariate analysis showed that initial metastasis, bone metastasis, and liver metastasis were independent prognostic factors for reduced PFS, whereas poor performance status, initial metastasis, and bone metastasis were prognostic for reduced OS. Application of a previous prognostic model showed that observed PFS and OS survival curves for patients in various risk groups differed significantly (P?Conclusions A 3-week regimen of S-1 plus cisplatin was active and well tolerated as first-line treatment in patients with AGC. Disease status and bone metastasis were the most important prognostic factors.     

A phase II study of docetaxel and oxaliplatin combination in recurrent gastric cancer patients after fluoropyrimidine and/or cisplatin adjuvant treatment: a Korean Cancer Study Group Protocol ST06-02

Background

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.

Methods

Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35?mg/m²) intravenously on day 1 and 8 plus oxaliplatin (100?mg/m²) intravenously on day 1 every 3?weeks until disease progression or unacceptable toxicity.

Results

A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6?months (range, 1–48?months) were enrolled in this trial; 22 (64.7?%) patients had been exposed to both agents. Their median age was 58?years (range, 50–68?years). The overall response rate was 55.9?% (95?% confidence interval (CI), 38.3–73.5?%), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5?months (range, 9.2–50.7?months), the median progression-free survival for all patients was 5.3?months (95?% CI, 4.4–6.1?months) and the median overall survival was 13.8?months (95?% CI, 11.1–16.4?months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1?%) and diarrhea (17.6?%), respectively. Five patients (14.7?%) experienced febrile neutropenia.

Conclusions

Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.     

Sequential chemotherapy with cisplatin, leucovorin, and 5-fluorouracil followed by docetaxel in previously untreated patients with metastatic gastric cancer: a phase II study

Background

The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) has demonstrated a survival advantage over cisplatin and 5-FU, but with substantial hematological toxicity. We aimed to evaluate the efficacy and toxicity of a sequential regimen with cisplatin, leucovorin, and 5-FU (PLF) followed by docetaxel in metastatic gastric cancer patients.

Methods

Treatment consisted of 4 cycles of biweekly PLF (cisplatin 50?mg/m² as a 30-min infusion on day 1, leucovorin 200?mg/m² in a 2-h infusion, and 5-FU 2,800?mg/m² in a 48-h continuous infusion starting on day 1) followed, in cases of response or stable disease, by 3 cycles of docetaxel (75?mg/m², every 3?weeks).

Results

Thirty-four patients were enrolled, with an average age of 64?years (range 34–69). The main cumulative grade 3–4 toxicities were: neutropenia (38.2%), febrile neutropenia (11.8%), and fatigue (14.7%). After the planned 7 cycles of treatment, the overall response rate was 38.2% (95% confidence interval [CI] 21.9–54.6), with 3 complete and 10 partial responses. Median progression-free survival and overall survival were 4.8 and 10.6?months, respectively.

Conclusions

For patients with metastatic gastric cancer, the sequential administration of cisplatin, leucovorin, 5-FU, and docetaxel may be an effective palliative option and offers a far more favorable toxicity profile than the simultaneous use of docetaxel, cisplatin, and 5-FU.     

Phase II study of irinotecan and cisplatin with concurrent split-course radiotherapy in limited-disease small cell lung cancer

Background

Irinotecan and cisplatin are one of active regimens for patients with extensive-stage small cell lung cancer (SCLC). To determine the efficacy and toxicity of irinotecan and cisplatin with concurrent split-course thoracic radiotherapy in limited-disease (LD) SCLC, we conducted a phase II study.

Patients and methods

Thirty-four patients fulfilling the following eligibility criteria were enrolled: chemotherapy-na?ve, good performance status (PS 0–1), age ≤75, LD-SCLC, and adequate organ function. The patients received irinotecan 40?mg/m² i.v. on days 1, 8, and 15, and cisplatin 60?mg/m² i.v. on day 1. Four cycles of chemotherapy were repeated every 4?weeks. Split-course thoracic radiotherapy of once-daily 2?Gy/day commenced on day 2 of each chemotherapy cycle, with 26 and 24?Gy administered in the first and second cycles, respectively.

Results

Thirty-four patients were eligible and assessable for response, toxicity, and survival. Patients’ characteristics were as follows: male/female?=?29/5; PS 0/1?=?18/16; median age (range)?=?67 (50–73); and stage IB/IIA/IIB/IIIA/IIIB?=?2/2/3/16/11. The overall response was 100?% (CR 8, PR 26). Grade 4 leukopenia, neutropenia, grade 3–5 pneumonitis, diarrhea, and esophagitis occurred in 24, 38, 6, 3, and 0?%, respectively. There were 2 treatment-related deaths from pneumonitis. The median time to tumor progression was 14.3?months. The median overall survival time and the 2- and 5-year survival rates were 44.5?months, 66.7 and 46.1?%, respectively. No tumor progression was observed in patients with CR.

Conclusion

Irinotecan plus cisplatin with concurrent split-course thoracic radiotherapy was effective and tolerable in untreated LD-SCLC.     

Combination chemotherapy with paclitaxel, cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma: a multicenter prospective study

Objective:To evaluate the efficacy and toxicity of the combination regimen of paclitaxel,cisplatin and 5-FU(PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction(EGJ) adenocarcinoma in China.Methods:The patients were treated with paclitaxel 150mg/m2 on d1;fractionated cisplatin 15mg/m 2 and continuous infusion 5-FU 600mg/(m2·d) intravenously on d1-d5 of a 21-d cycle until disease progression or unacceptable toxicities.Results:Seventy-five patients have been enrolled,among which,41 received PCF regimen as the first-line therapy(group A) and 34 received the regimen as the second-line therapy(group B) with the median age of 59 years old and Karnofsky performance status(KPS) score ≥80.Toxicities were analyzed in all 75 patients.Seventy-one patients were evaluable for efficacy.The median overall survival(mOS) was 12.0 months(95% CI:7.9-16.2 months) in group A and 7.3 months(95% CI:4.3-10.3 months) in group B,respectively.The median progression-free survival(mPFS) was 5.7 months(95% CI:4.1-7.2 months) and 5.0 months(95% CI:3.1-6.9 months),respectively.The response rate(CR+PR) was 40%(16/40;95% CI:24.9-56.7%) in group A and 22.6%(7/31;95% CI:9.6-41.1%) in group B.Major grade 3 or 4 adverse events include neutropenia(41.3%),febrile neutropenia(9.3%),nausea/anorexia(10.7%),and vomiting(5.3%).There was no treatment-related death.Conclusions:The combination chemotherapy with PCF is active and tolerable as first-line and secondline therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma.The response and survival of PCF are same as those of DCF,but the tolerance is much better.     

The efficacy and safety of gemcitabine plus paclitaxel combination first-line therapy for Japanese patients with metastatic breast cancer including triple-negative phenotype

Purpose

Gemcitabine (GEM)?Cpaclitaxel combination therapy has been confirmed as a standard therapy for metastatic/recurrent breast cancer (MBC) in Western countries. This study was conducted to assess the efficacy and safety of GEM?Cpaclitaxel combination therapy in Japanese MBC patients.

Methods

Patients were administered paclitaxel 175?mg/m² on day 1, and GEM 1,000 or 1,250?mg/m² on days 1 and 8 of 21-day cycle. The primary endpoint of this study was overall response rate; secondary endpoints were duration of response, time to progression, survival time and rate.

Results

Paclitaxel 175?mg/m² plus GEM 1,250?mg/m² was determined as the recommended dose. A total of 56 patients received 506 cycles of treatment (median: 7.5 cycles) with a relative dose intensity of 79.6% for GEM and 85.8% for paclitaxel. The response rate was 44.6% (25/56 patients), median time to progression 8.6?months and median survival time 27.1?months. In triple-negative patients, the response rate was 35.7% (5/14 patients), and the median time to progression was 6.0?months. The most frequent grade????3 toxicities were neutropenia (82.1%), leukopenia (62.5%) and ALT increase (14.3%).

Conclusions

This study confirmed the efficacy and safety of GEM?Cpaclitaxel combination therapy in Japanese MBC patients.     

Phase I and pharmacologic study of BNP7787, a novel chemoprotector in patients with advanced non-small cell lung cancer

Purpose

We conducted a phase I trial of BNP7787 (disodium 2,2??-dithio-bis-ethane sulfonate, Tavocept?), a novel chemoprotective and antitumor enhancing agent administered in combination with paclitaxel and cisplatin. The primary aim was to determine a safe and potentially efficacious BNP7787 dose for preventing and mitigating paclitaxel- and cisplatin-induced toxicities and to evaluate for preliminary evidence of efficacy of treatment.

Patients and methods

Twenty-two patients with stage IIIB/IV non-small cell lung cancer (NSCLC) received BNP7787 alone 1 week before co-administration of BNP7787 with paclitaxel followed by cisplatin. Twenty-one patients were treated with BNP7787 in escalating doses of 4.1?C41.0?g/m² concurrently with paclitaxel 175?mg/m² and cisplatin 75?mg/m² every 3?weeks.

Results

The appropriate dose was determined to be 18.4?g/m² of BNP7787 although no dose-limiting toxicity was observed up to 41.0?g/m². Mild intravenous site discomfort, thirst, and nausea were the most common toxicities. One patient developed grade 2 skin rash, which was severe enough to preclude further study treatment. The AUC_0-inf of the metabolite mesna was approximately 6.3% of the AUC_0-inf of BNP7787. Co-administration of paclitaxel and cisplatin did not appear to influence the pharmacokinetics of BNP7787 and mesna. The overall response rate was encouraging; 43% including 11 patients with prior chemotherapy.

Conclusions

The recommended dose for phase II/III studies is 18.4?mg/m² of BNP7787 in combination with paclitaxel and cisplatin. Further studies are warranted to assess whether BNP7787 prevents and mitigates common and serious paclitaxel- and cisplatin-related side effects and enhances the efficacy of paclitaxel and cisplatin in advanced NSCLC patients.     

A pilot feasibility study for cisplatin plus S-1 for the treatment for advanced or recurrent cervical cancer

Purpose

To evaluate the feasibility of a cisplatin and S-1 combination regimen for the treatment for metastatic and recurrent cervical cancers, we performed this study prior to a randomized phase III trial to evaluate the clinical benefits of a cisplatin and S-1 combination regimen compared with cisplatin alone.

Methods

Cisplatin (50 mg/m², intravenously on day 1) and S-1 (80–120 mg/m², orally twice a day between days 1 and 14) were administered every 21 days for 6 cycles in patients with advanced or recurrent uterine cervical cancer.

Results

A total of 10 patients were enrolled in this trial. A total of 46 treatment cycles (median 6; range 1–6) were administered. All grade 3 or 4 hematologic toxicities were recorded in the 6 patients: 2 patients experienced anemia, 5 experienced neutropenia, 1 experienced thrombocytopenia, and 2 experienced febrile neutropenia. All grade 3 non-hematologic toxicities were recorded in the 6 patients, and no grade 4 non-hematologic toxicities occurred; the most frequent toxicities were hyponatremia in 3 patients, diarrhea in 2 patients, and infection in 2 patients. The patients with grade 3 diarrhea had received prior radiotherapy. All the patients recovered from the toxicities after receiving appropriate supportive care, and no treatment-related deaths occurred. Five patients (50 %) achieved a partial response, and 1 patient (10 %) had a stable disease.

Conclusion

A cisplatin and S-1 combination regimen was feasible for patients with recurrent cervical cancer. Since patients who receive prior radiotherapy may experience severe diarrhea, these patients may require an S-1 dose reduction.     

Combination chemotherapy with S-1 plus cisplatin for gastric cancer that recurs after adjuvant chemotherapy with S-1: multi-institutional retrospective analysis

Background

It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy.

Methods

We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy.

Results

In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1?months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4?months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8?months, and the median overall survival (OS) was 12.2?months. Compared with patients with an RFI of <6?months (n?=?25), patients with an RFI of ≥6?months (n?=?27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2?months, respectively), and longer overall survival (7.3 vs. 16.6?months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6?months was still significantly associated with PFS and OS.

Conclusions

S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6?months.     

Chemotherapy with gemcitabine, cisplatin, and docetaxel in the treatment for patients with muscle-invasive bladder cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG)

Purpose

To assess the antitumor activity and toxicity of gemcitabine, cisplatin, and docetaxel (GCD) regimen in patients with locally advanced or metastatic urothelial cancer.

Patient and methods

Chemotherapy-na?ve patients, aged ??70?years with measurable or evaluable disease and a performance status (PS) of 0?C2 were treated with sequential cisplatin 80?mg/m² (d1), gemcitabine 1,100?mg/m² (d1 and d14), and docetaxel 80?mg/m² (d14) every 28?days.

Results

Sixty patients with an ECOG PS of 0?C2 were enroled. Most (71.7%) patients had stage IV disease. A median number of 4 chemotherapy cycles per patient (range, 1?C9) was administered. Eight (13.3%) patients achieved a CR and 16 (26.7%) a partial response (PR) (intention-to-treat: ORR 40%; 95% CI 27.6?C52.4%). Thirteen (21.7%) and 23 (38.3%) patients experienced stable and progressive disease, respectively. The median time to progression (TTP) was 7.7?months (range, 0.7?C43.4), and the median overall survival 21.4?months (range, 0.7?C68.6). Grade 3 and 4 neutropenia occurred in 27 (45%) patients and grade 3 and 4 thrombocytopenia in five (8.3%). Three (5%) patients developed febrile neutropenia. There were no treatment-related deaths. Severe non-haematological toxicity was infrequent.

Conclusions

The GCD combination is an active and well-tolerated regimen in patients with chemotherapy-naive locally advanced or metastatic TCC and merits to be further investigated.     

Phase I/II and pharmacokinetic study of S-1 and oxaliplatin in previously untreated advanced gastric cancer

Background

We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced gastric cancer (AGC).

Methods

Oxaliplatin was fixed at a dose of 130 mg/m² on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m² per day from 70 mg/m² per day up to 100 mg/m² per day. Pharmacokinetic analyses were performed following a single dose of S-1 on D-5 and D1 of the first cycle.

Results

In phase I (n = 18), MTD was not defined. In phase II (n = 47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0–9.2 months) and the median overall survival was 12.5 months (95% CI 9.2–15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle.

Conclusions

The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.