Application of prolonged microdialysis sampling in carboplatin-treated cancer patients

Purpose  To determine the dose-limiting toxicity (DLT) and activity of combination with docetaxel and S-1 on unresectable gastric cancer. Patients and methods  Docetaxel was administered intravenously on day 1 and S-1 was administered orally on days 1–14, every 3 weeks. Doses of each drug in phase I study were docetaxel 60–75 mg/m² and S-1 60–80 mg/m². A phase II study was conducted with the recommended dose (RD) based on phase I. Results  Sixty-five patients (median age 54 years) were enrolled. The DLTs were neutropenia with fever or stomatitis. The RD was docetaxel 75 mg/m² and S-1 60 mg/m². Two patients (aged 66 and 64 years) developed septic shock during the initial part of phase II study. A phase I study at lower dose (docetaxel 60 mg/m² and S-1 80 mg/m²) was conducted for patients older than 60 years, and this dose was determined as the RD for these patients. In the phase II study, frequent grade 3/4 toxicities were neutropenia (47%) and febrile neutropenia (26%). The overall response rate was 50% (95% CI, 35–66%) and median survival was 15.3 months (95% CI, 10.0–20.6 months). Conclusions  Combination with docetaxel and S-1 was active against advanced gastric cancer and gave manageable toxicities. Supported in part by a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (0412_CR01_0704_0001).     

Phase I/II study of intraperitoneal docetaxel plus S-1 for the gastric cancer patients with peritoneal carcinomatosis

Purpose

We designed a phase I/II trial of intraperitoneal (IP) docetaxel plus S-1 to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate its efficacy and safety in gastric cancer patients with peritoneal carcinomatosis (PC).

Methods

Patients with PC confirmed by laparoscopy or laparotomy received IP docetaxel on days 1 and 15 and S-1 (80 mg/m²) on days 1–14 every 4 weeks.

Results

In the phase I part (n = 12), each cohort received escalating doses of docetaxel (35–50 mg/m²); the MTD was determined to be 50 mg/m² and the RD was determined to be 45 mg/m². Dose-limiting toxicities included grade 3 febrile neutropenia and grade 3 diarrhea. In the phase II part (n = 27), the median number of courses was 4 (range 2–11). The 1-year overall survival (OS) rate was 70 % (95 % confidence interval 53–87 %). The overall response rate was 22 % and peritoneal cytology turned negative in 18 of 22 (81 %) patients. The most frequent grade 3/4 toxicities included anorexia (19 %), neutropenia (7 %), and leukopenia (7 %).

Conclusion

IP docetaxel plus S-1 is active and safety in gastric cancer patients with PC.     

Phase I trial of weekly docetaxel with a 4-weekly cisplatin administration in patients with advanced gastric carcinoma

The docetaxel-cisplatin combination is active against several tumors including gastric cancer but it is followed by severe myelosuppression. Recent experience with weekly taxanes has demonstrated a mild myelotoxicity with high dose intensity. We investigated in a phase I study a weekly schedule of docetaxel on days 1, 8 and 15 and cisplatin on day 1 every 4 weeks in 19 patients with advanced gastric cancer with no prior chemotherapy. Cohorts of patients were treated with escalating doses of docetaxel (starting dose 30 mg/m² per week and increments of 10 mg/m² per week) and cisplatin (starting dose 70 mg/m² and increments of 5 mg/m²). Febrile neutropenia was the only dose-limiting event occurring in four (20%) patients; the dose-limiting toxicity was reached at dose level three (docetaxel 40 mg/m² per week and cisplatin 75 mg/m²). The maximum-tolerated dose was 40 mg/m² per week for docetaxel and 70 mg/m² every 4 weeks for cisplatin. Grade 3/4 neutropenia occurred in six patients (30%); early death occurred in one patient with septic shock because of neutropenia and another with acute coronary ischemia. Two (11%) complete and two (11%) partial responses were documented (ORR 22%; 95% CI 3–39%), with a median response duration of 5 months and median time to progression of 7 months. In conclusion, the combination of weekly docetaxel plus cisplatin is feasible with moderate toxicity and merits further investigation in phase II studies in advanced gastric cancer.Presented as an abstract at the 15th International Congress on Anti-Cancer Treatment, Paris, 9–12 February 2004.     

A phase I-II study of gemcitabine and docetaxel in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

Background: Gemcitabine and docetaxel have been claimed to be active single agents in advanced pancreatic cancer. We determined the maximum tolerable dose of docetaxel combined with a weekly fixed dose of gemcitabine and assessed the activity of this combination in advanced pancreatic cancer.Patients and methods: Phase I. Patients were treated with gemcitabine on days 1 and 8, every three weeks, at a fixed dose of 1,000 mg/m²; docetaxel was given at escalating doses starting from 70 mg/m² on day 8. Phase II. In accord with the optimal two-stage phase II study design, 18 patients were treated with gemcitabine (1000 mg/m²) and the maximum tolerable dose of docetaxel (70 mg/m²).Results: Phase I. Dose-limiting toxicities occurred at the second dose level of docetaxel (80 mg/m²), with all three patients developing grades 3 or 4 neutropenia. Consequently, the dose tested in the phase II study was 70 mg/m². Phase II. In the 18 patients enrolled in the study, we registered only one partial response. The time to progression was 3 months, and the median treatment survival was 5.4 months. Grade 3–4 toxicities consisted of neutropenia (three episodes) and thrombocytopenia (two episodes). Furthermore, 10 patients complained of grade 3 fatigue.Conclusions: The addition of docetaxel to gemcitabine does not appear to be useful in advanced pancreatic cancer, since gemcitabine alone achieves similar results.     

Dose-finding study of docetaxel, oxaliplatin, and S-1 for patients with advanced gastric cancer

Purpose  To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy on metastatic gastric cancer. Patients and methods  Docetaxel and oxaliplatin were administered intravenously on day 1 and S-1 was administered orally on days 1–14 of every 21-day cycle. The doses of docetaxel/oxaliplatin/S-1 in the phase I study were level −1A, 52.5/80/60 mg/m²; level −1B, 52.5/80/80 mg/m²; level 1A, 52.5/105/80 mg/m²; level 1B, 52.5/130/80 mg/m²; level 2A, 60/105/80 mg/m²; level 2B, 60/130/80 mg/m²; level 3A, 67.5/105/80 mg/m²; level 3B, 67.5/130/80 mg/m²; level 4A, 75/105/80 mg/m²; level 4B, 75/130/80 mg/m². Results  Nine patients were enrolled. One of six patients at level 1A and two of three patients at level 1B developed dose-limiting toxicity (febrile neutropenia) during the initial two cycles. Therefore, the doses used at levels 1B and 1A were defined as the MTD and RD, respectively. All patients were evaluated for toxicity and response. Six partial responses were noted, and the overall response rate was 67%. Conclusion  The RD of the DOS regimen in patients with advanced gastric cancer was docetaxel 52.5 mg/m² and oxaliplatin 105 mg/m² on day 1 and S-1 80 mg/m² on days 1–14 of every 21-day cycle. A phase II study using the RD is currently underway.     

Phase I-II study of irinotecan combined with mitomycin-C in patients with advanced gastric cancer.

Background:Irinotecan (CPT-11) shows synergism withmitomycin-C (MMC) in a preclinical setting. The goals of this study wereto determine the maximum tolerated dose (MTD), the dose limitingtoxicity, the recommended dose (RD), and preliminary anti-tumor activityin a combined CPT-11 and MMC treatment of advanced gastric cancer. Patients and methods:The study was designed to evaluateescalated doses of CPT-11 and MMC administered every two weeks. Fiveescalating dose levels were studied (CPT-11/MMC: 100/5; 125/5; 150/5;150/7; 150/10 mg/m²). Results:Thirty-onepatients were enrolled. Thirty patients were assessable for toxicity andtumor response for 89 treatment cycles. The median age was 60 years(32–73 years), and most patients (90%) had a performancestatus of 0 to 1. Fourteen patients were previously treated and 17 werechemotherapy-naive. The MTD was CPT-11 150 mg/m² plus MMC 10mg/m², in which all three patients experienced grade 4neutropenia, including one episode of prolonged and one of febrileneutropenia, and one patient experienced grade 3 diarrhea during thefirst cycle. Fifteen partial responses were observed. Conclusions:The RD based on this phase I–II study wasCPT-11 150 mg/m² plus MMC 5 mg/m² administeredevery two weeks. This combination demonstrates promising activityagainst advanced gastric cancer and warrants further investigation inanother phase II study.     

Phase I dose-escalation study of docetaxel, nedaplatin, and 5-fluorouracil combination chemotherapy in patients with advanced esophageal cancer

More effective protocols are needed for unresectable and recurrent esophageal cancer. Therefore, we conducted a phase I trial to establish the recommended dose of docetaxel, nedaplatin, and 5-fluorouracil (DNF) as combination chemotherapy. Fourteen patients with esophageal cancer were enrolled and received DNF combination therapy at different dose levels according to the treatment and examination plan. Dose-limiting toxicities (DLTs) included febrile neutropenia. DLTs occurred in 3/5 patients at level 4. The recommended doses (level 3) of DNF were 60 mg/m² (day 1), 70 mg/m² (day 1), and 700 mg/m² (days 1–5), respectively, given at 3-week intervals. In conclusion, DNF combined chemotherapy for advanced esophageal cancer was associated with relatively minor adverse events and was safely administered at the recommended dose. A phase II study is now underway.     

A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m²/day (days 1–14), while the dose for paclitaxel increased by 10 mg/m² for every three patients, with a starting dose of 100 mg/m² and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m² of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m² of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38°C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m² and 80 mg/m², respectively.     

Phase I study of docetaxel and cisplatin for patients with previously untreated metastatic non-small-cell lung cancer: a Japanese cooperative study

Background. Docetaxel is one of the most active agents used in the treatment of advanced non-small-cell lung cancer. This phase I study was performed to determine the toxicities, maximum tolerated dose, and pharmacokinetics of the combination of docetaxel and cisplatin in patients with non-small-cell lung cancer, and to recommend a dose for phase II study. Methods. Patients were required to have previously untreated metastatic non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 2 or less, be aged between 15 and 74 years, to have a measurable lesion, and to have adequate organ function. Treatment consisted of 1-h infusion of docetaxel on day 1, followed by 2-h infusion of cisplatin (3 h after docetaxel) at the following docetaxel/cisplatin (mg/m²) dose levels: 50/50, 60/50, 60/60, 60/70, and 60/80. At least three patients were accrued at each dose level. Treatment was repeated every 3 to 4 weeks for responders. Administration of granulocyte-colony stimulating factor was permitted when leukocytopenia or neutropenia of grade 3 or more occurred. Results. Of the 29 patients entered, all were assessable for toxicity and response, but 2 were excluded from analyses of dose-limiting toxicity and maximum tolerated dose. Neutropenia (grade 4, for 3 days or more; n = 1), hepatic dysfunction (grade 3 or more; n = 2) and renal dysfunction (grade 2 or more; n = 3) were observed as dose-limiting toxicities. However, the maximum tolerated dose was not detected, even at the highest dose examined. Tumor response occurred in 13 of the 29 patients (45%; 95% confidence interval; 26%–64%). The pharmacokinetic profiles of docetaxel and cisplatin (n = 17) were similar to those observed after the administration of each dose as a single agent. Conclusion. Docetaxel/cisplatin doses of 60/80 mg/m² were recommended for phase II study, because grade 4 neutropenia occurred in 50% or more patients at docetaxel/cisplatin dose levels of 60/60 mg/m² and above, and the doses of these drugs were restricted to within the approved dose ranges for single-agent use in Japan. The responses observed in this phase I study suggest a high degree of activity of this combination against previously untreated advanced non-small-cell lung cancer and warrant a phase II study at the recommended dose level. Received: February 29, 2000 / Accepted: June 22, 2000     

A phase I trial of docetaxel and gemcitabine in patients with advanced cancer

Background:Docetaxel and gemcitabine are active in a broad rangeof malignancies. The objective of this phase I trial was to determine themaximally tolerated doses of the combination of docetaxel and gemcitabine. Patients and methods:Patients with advanced cancer, WHOperformance status 0–2, who had received up to one prior chemotherapyregimen were treated with gemcitabine on days 1 and 8 and docetaxel on day 8repeated every 21 days. Prophylactic ciprofloxacin was commenced on day 11 ofeach cycle and continued until the neutrophil count reached 1.0 ×10⁹/l. G-CSF was not administered. Dose levels studied weredocetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200 and 100/1200mg/m². Results:Thirty-nine patients were entered and all were assessablefor toxicity. The highest administered dose level was 100 mg/m²docetaxel and 1200 mg/m² gemcitabine with dose limiting toxicitiesof febrile neutropenia, grade 4 neutropenia 7 days, grade 4thrombocytopenia, grade 3 stomatitis and/or grade 3 fatigue in three out ofsix patients. Treatment was well tolerated (40 cycles) in the 10 patientstreated at the recommended dose level (85/1200) with only a single episode offebrile neutropenia and grade 3 or 4 non-hematologic toxicity was infrequent.There was no significant pulmonary toxicity. Responses were seen in a rangeof malignancies including non-small-cell lung cancer. Conclusions:The recommended dose level of 85 mg/m²docetaxel and 1200 mg/m² gemcitabine has a favourable toxicityprofile and is suitable for further investigation in phase II trials. Thisnon-platinum containing regimen warrants further investigation as a potentialalternative to platinum containing regimens in non-small-cell lung cancer andother malignancies.     

Phase I trial of dose escalation of capecitabine combined with fixed docetaxel in previously treated patients with non-small cell lung cancer

Objective

Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer (NSCLC). Due to absence of phase I trial in China, we conducted this study to define the maximum-tolerated dose (MTD) of capecitabine with fixed docetaxel for Chinese patients with previously treated NSCLC.

Methods

Previously treated patients with NSCLC were entered into this study. Escalating doses of capecitabine with fixed docetaxel were administered in a modified Fibonacci sequence. The initial doses were capecitabine 625 mg/m², bid, on days d5?Cd18, and docetaxel 30 mg/m² on days 1 and 8, respectively. The regimen was repeated every 21 days. If no dose-limiting toxicity (DLT) was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be one dose level below the level at which DLT appeared.

Results

Eighteen patients received 67 cycles at capecitabine of level I (1250 mg/m², divided into 625 mg/m², bid) and level II (1500 mg/m², 750 mg/m², bid). The most common toxicities were neutropenia, hand and feet syndrome, fatigue and nausea. Eight DLTs occurred in 5 patients in the whole group, including 1 DLT in dose level I and 7 DLTs in dose level 2. Since 4 of 6 patients in level II experienced DLTs, we declared thus level I was MTD.

Conclusion

MTD of our phase I trial was capecitabine of 1250 mg/m²/d combined with docetaxel of 30 mg/m²/wk. This combination regimen was well tolerated for previously treated patients with NSCLC. The efficacy of this schedule is currently being further evaluated in a prospective phase II trial.     

Docetaxel and cisplatin in patients with advanced or recurrent gastric cancer: a multicenter phase I/II study

Background: Because docetaxel and cisplatin are both active against gastric cancer and have different mechanisms of action, this combination may provide additive or synergistic effects against gastric cancer. This article presents a phase I study designed to determine the recommended dose of cisplatin combined with a fixed dose of docetaxel, and a subsequent phase II study that evaluated the clinical efficacy and feasibility of this combination regimen. Methods: Patients enrolled in the study had to have histologically confirmed advanced or recurrent gastric cancer with measurable disease and adequate organ function, and to be aged 20 to 75 years, with a performance status (PS) of 0 to 2. In the phase I study, docetaxel was administered at a fixed dose of 60 mg/m² on day 1. Cisplatin was also administered on day 1, at dose levels of 60, 70, and 80 mg/m². Where dose-limiting toxicities were not observed in more than 33.3% of patients, three patients were accrued for each dose level. Results: Recommended doses for the phase II evaluation were determined to be 60 mg/m² of docetaxel and 80 mg/m² of cisplatin. Although grade 3 or more severe leukopenia and neutropenia were observed in 71.4% and 82.1% of the patients, respectively, nonhematological toxicities were not severe. The overall response rate at the recommended dose level was 25.0% (7/28 patients), and the rate was 40% (6/15) for patients with liver metastases. The median survival time was 9.7 months and the 1-year survival rate was 39.3%. Conclusion: Although this study failed to demonstrate a high response rate, this regimen was feasible and might be of value in further investigations in respect to the relatively high response rate in patients with liver metastasis and the favorable survival. Received: March 26, 2002 / Accepted: June 28, 2002 Acknowledgments We are grateful to Drs. T. Taguchi, M. Yoshida, K. Nagao, and S. Yoshida for their helpful advice and N. Hirabayashi, W. Koizumi, and K. Shirao for their extramural review during the study. Offprint requests to: Y. Mitachi     

High Efficacy of Paclitaxel and Doxorubicin as First-Line Therapy in Advanced Breast Cancer: A Phase I-II Study

Abstract

The aim of this study was to define the maximum tolerated dose (MTD) of paclitaxel (TAX) in combination with doxorubicin (ADM). To evaluate the efficacy and tolerability of this combination, TAX was administered in escalating doses of 30 mg/m², starting from 120 mg/m², by 1 hour continuous infusion, per group of three patients; ADM was administered at a fixed dose of 50 mg/m², 24 hours before administering TAX (phase I). The combination was recycled every 3 weeks. In phase II, TAX was administered at the MTD defined in phase I.

Thirty-six women were enrolled. The MTD of TAX was 220 mg/m². Objective responses were observed in 28/34 (82%) assessable patients. The median progression-free survival was 11.8 months and overall survival 27.8 months. The main clinical toxicity was neutropenia (grade III-IV) of short duration (94%). Two patients developed cardiac toxicity.

The combination TAX+ADM is very effective in advanced breast cancer.     

A phase 1 study of pralatrexate in combination with paclitaxel or docetaxel in patients with advanced solid tumors.

PURPOSE: Pralatrexate is a rationally designed antifolate with greater preclinical antitumor activity than methotrexate. Pralatrexate was synergistic with paclitaxel and with docetaxel in mouse xenograft experiments. This phase 1 study was designed to determine the maximum tolerated dose and toxicity of pralatrexate plus paclitaxel or docetaxel in patients with advanced cancer. EXPERIMENTAL DESIGN: Pralatrexate was administered i.v. every 2 weeks (days 1 and 15) in a 4-week cycle. Depending on the taxane used and dose being tested, the taxane was administered on days 1 and 15; days 2 and 16; or days 1, 8, and 15. In the latter part of the study, patients in the docetaxel arm were treated with vitamin B(12) and folic acid supplementation to mitigate toxicity and allow pralatrexate dose escalation. RESULTS: For the combination of pralatrexate plus paclitaxel without vitamin supplementation, dose-limiting stomatitis and peripheral neuropathy were encountered at the lowest dose levels tested. For pralatrexate plus docetaxel plus vitamin supplementation, pralatrexate 120 mg/m(2) plus docetaxel 35 mg/m(2) administered on the same day every other week was defined as the maximum tolerated dose and schedule, with dose-limiting toxicities at higher dose combinations including stomatitis and asthenia. Significant antitumor activity was observed for this combination in patients with non-small-cell lung cancer. CONCLUSIONS: Pralatrexate (120 mg/m(2)) plus docetaxel (35 mg/m(2)) plus vitamin supplementation is well tolerated with signs of efficacy against non-small-cell lung cancer that merit phase 2 testing.     

Phase I dose escalation study of docetaxel with a fixed dose of S-1 in combination chemotherapy for advanced gastric cancer

Background  The primary objectives of this study were to estimate the maximum-tolerated dose (MTD) of docetaxel in combination with a fixed dose of S-1 and to determine the recommended dose (RD). Patients and methods  Patients with histologically proven gastric carcinoma with metastatic or locally advanced inoperable disease were eligible. Patients received intravenous docetaxel starting at 40 mg/m² (dose level 1), and stepwise dose increases to 50, 60, and 70 mg/m² were planned for successive patient cohorts (dose levels 2, 3, and 4, respectively) over 1 h on day 1 and oral S-1 administered at a fixed dose of 40 mg/m² twice daily on days 1–14, both drugs every 21 days. Results  A total of 13 patients were enrolled into this trial. All three patients at dose level 3 developed dose-limiting toxicities (DLT), and this level was declared to be the MTD. Hence, level 2 (docetaxel 50 mg/m²) was declared to be the RD for the next study. As 9 of the 13 enrolled patients responded to treatment, the overall objective response rate was 69.2% (95% CI, 44.1–94.3%). The median time to progression was 8.38 months (range 1.44–8.51) and the overall survival duration was 9.9 months (range 0.62–11.57). The most common grade 3/4 toxicity of docetaxel plus S-1 was neutropenia, which was tolerable and manageable. Conclusion  This regimen showed encouraging activity and a manageable safety profile in advanced gastric carcinoma and could be used in further randomized studies.     

A Prospective Phase I/II Study of Docetaxel,Cisplatin and Continuous Capecitabine in Advanced Oesophago-Gastric Cancer (NWCOG-3)

Aims

This open-label prospective phase I/II dose-escalation study determined the maximum tolerated dose (MTD) and then evaluated response, safety and feasibility of a novel combination of docetaxel, cisplatinum and capecitabine (DCC) in chemotherapy-naive patients with advanced oesophago-gastric carcinoma.

Phase I/II study of 3-week combination of S-1 and cisplatin chemotherapy for metastatic or recurrent gastric cancer

Purpose To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC). Patients and methods Cisplatin was fixed at a dose of 60 mg/m² on day 1 (D1) and the starting dose of S-1 was 60 mg/m²/day (30 mg/m² bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m² bid up to 100 mg/m²/day (level V) unless the MTD was achieved. Results Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m²/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m²/day (N = 23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6–6.0 months) with a median OS of 10.0 months (95% CI, 5.1–14.8 months). Grade 3–4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%). Conclusions The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.     

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.     

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.     

Phase I/II trial of a biweekly combination of S-1 plus docetaxel in patients with previously treated non-small cell lung cancer (KRSG-0601)

Background:

Combination of S-1, an oral fluorouracil derivative, plus docetaxel against non-small cell lung cancer (NSCLC) showed promising efficacy but clinically problematic emesis. A phase I/II study utilising a new schedule for this combination was conducted.

Methods:

A biweekly regimen of docetaxel on day 1 with oral S-1 on days 1–7 was administered to previously treated NSCLC patients. Doses of docetaxel/S-1 were escalated to 30/80, 35/80, and 40/80 mg m⁻², respectively, and its efficacy was investigated at the recommended dose below maximum tolerated dose (MTD).

Results:

In phase I study employing 13 patients, dose-limiting toxicities were febrile neutropenia and treatment delay, with the respective MTDs for docetaxel 40 mg m⁻²/S-1 80 mg m⁻². In the phase II study, 34 patients were treated with docetaxel 35 mg m⁻²/S-1 80 mg m⁻² for a median cycle of 6. The response and disease control rates were 34.3% (95% confidence interval (CI), 18.6–50.0%) and 62.9% (95% CI, 46.8–72.9%), respectively. Median progression-free survival was 150.5 days. Haematologic grade 4 toxicities were observed in neutropenia (11.8%) and thrombocytopenia (2.9%). Regarding non-haematologic toxicities, including emesis, there were no grade 3/4 side effects.

Conclusion:

Combination of 1-week administration of S-1 with biweekly docetaxel is safe and active for NSCLC.