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.     

The effect of gemcitabine/paclitaxel chemotherapy on the survival of patients with metastatic urothelial cancers

Background

To evaluate the survival benefit of gemcitabine and paclitaxel (GT) chemotherapy for patients with metastatic urothelial cancer (UC), a retrospective analysis was performed to compare the overall survival in two periods: before (group I) and after (group II) the introduction of GT chemotherapy.

Patients and methods

Eighty-five patients with metastatic UC were treated with MEC/MVAC (methotrexate, epirubicin, and cisplatin / methotrexate, vinblastine, doxorubicin, and cisplatin) or GT between 1995 and 2007. The response rate, maintenance rate, maintenance duration of each regimen, and the survival times of responding patients in each group were evaluated retrospectively.

Results

The median survival of patients in group ΙI (20 months) was significantly longer than that for group I (13 months) (p = 0.03). Especially in patients with a favorable response (CR/PR) to induction chemotherapy, the median survival period was significantly different between group Ι and group II (median 15 and 28 months, respectively; p = 0.02). The rate of the shift to maintenance chemotherapy when using GT chemotherapy was significantly higher than with MEC/MVAC chemotherapy alone (p < 0.05), and the cessation rate due to adverse effects was significantly lower when using GT chemotherapy (26.1%) than MEC/MVAC in group Ι (42.1%).

Conclusion

Our results demonstrated that the administration of GT chemotherapy may be useful to improve the survival of patients with metastatic UC. This effect was significant, especially among those who were sensitive to the induction course of first-line chemotherapy. The excellent tolerability of GT regimens mean that they may be suitable for maintenance chemotherapy.     

Paclitaxel in combination with carboplatin as salvage treatment in patients with castration-resistant prostate cancer: a Hellenic oncology research group multicenter phase II study

Introduction

To evaluate the efficacy and tolerance of biweekly paclitaxel and carboplatin combination in patients with castration-resistant prostate cancer.

Patients and methods

Patients were treated with paclitaxel at the dose of 135?mg/m² followed by carboplatin AUC 3 on day 1 every 2?weeks in cycles of 28?days.

Results

Thirty-eight patients with castration-resistant prostate cancer were enrolled, and all of them had received frontline chemotherapy with docetaxel and prednisone, while 24 (63.2?%) had received 2 or more prior chemotherapy regimens. In an intention-to-treatment analysis, a clinical and/or biochemical response (>50?% decline) was observed in 10 patients (26.3?%; 95?% CI, 12.3?C40.3?%), stable disease in 13 (34.2?%) and progressive disease in 15 (39.5?%). The median duration of response was 6.1?months (range, 1.0?C9.8), the median time to tumor progression (TTP) 3.6?months (95?% CI, 2.1?C5.2) and the median overall survival 9.9?months (95?% CI, 6.2?C13.6). The probability for 1-year survival was 43?%. Grade 3 and 4 neutropenia was observed in three (7.9?%) and nine (23.7?%) patients, respectively.

Conclusion

The biweekly administration of paclitaxel/carboplatin regimen in patients with castration-resistant prostate cancer is an active and well-tolerated regimen which merits to be further evaluated in the context of salvage treatment.     

Gemcitabine and docetaxel,an effective second-line chemotherapy for lung metastasis of urothelial carcinoma

Background

The objective of this study was to evaluate the efficacy of a gemcitabine and docetaxel (GD) combination as a second-line treatment for patients with metastatic urothelial carcinoma (UC) after failure of first-line treatment with platinum-based chemotherapy.

Methods

From June 2006 to January 2012, 38 patients with metastatic UC previously treated with platinum-based chemotherapy received GD therapy. This consisted of gemcitabine 800 mg/m² and docetaxel 40 mg/m² on days 1 and 8 of each 21-day cycle as second-line chemotherapy. All the patients were evaluated for toxicity and assessed every cycle by imaging. We analyzed the efficacy of GD as second-line chemotherapy in the follow-up study.

Results

The median number of GD treatment cycles was 4 (range 2–9); the objective response rate was 47.4 %; and the median progression-free survival and median overall survival were 4.1 and 10.8 months, respectively. Univariate and multivariate analyses on the GD treated group showed that the existence of lung metastases was the only prognostic factor for tumor response. Grade 3 treatment-related toxicity included neutropenia (31.6 %) and thrombocytopenia (15.8 %), and only one patient with grade 4 toxicity had thrombocytopenia (2.6 %).

Conclusions

The GD regimen as second-line chemotherapy was especially effective for lung metastatic UC and yielded favorable results in patients whose first-line platinum-based chemotherapy had failed. Given the safety and benefit profile seen in this study, a large prospective study is warranted to consider the potential utility of GD chemotherapy as a second-line for UC.     

Outcome, clinical prognostic factors and genetic predictors of adverse reactions of intermittent combination chemotherapy with docetaxel, estramustine phosphate and carboplatin for castration-resistant prostate cancer

Objectives

Docetaxel-based chemotherapy is effective in patients with castration-resistant prostate cancer (CRPC). This phase II study assessed the outcome and predictive factors for prognosis and toxicity following intermittent chemotherapy with docetaxel, estramustine phosphate, and carboplatin (DEC) in patients with CRPC.

Methods

Thirty-five patients were treated with a DEC regimen that consisted of a 28-day cycle of drugs as follows: docetaxel (60?mg/m² on day 1), carboplatin (AUC 5 on day 1) and estramustine phosphate (560?mg daily). Treatment was continued intermittently. The end point was to test the effect of DEC on the response rate and overall survival (OS). Statistical correlations between the outcomes and predictive factors, including clinical parameters and 8 single-nucleotide polymorphisms (SNPs) related to drug metabolism, were assessed.

Results

Prostate-specific antigen levels decreased by more than 30% in 65.7% of the patients. The median OS following DEC was 17.8?months, and the median total time of chemotherapy holiday was 7.7?months (range 1.7?C35.8). On multivariate analysis, serum lactate dehydrogenase (LDH) was an independent prognostic factor for OS (p?=?0.007). On SNP analysis, patients carrying the TT genotype of the ABCB1 C3435T polymorphism showed a significantly more severe leukocytopenia during the first cycle of DEC therapy compared to patients with the CC?+?CT genotype (p?=?0.036).

Conclusion

Combination chemotherapy with DEC has a potential effect on CRPC with acceptable toxicity. Serum LDH may be a promising predictor of prognosis, and the ABCB1 C3435T polymorphism may be a genetic predictor of the severity of leukocytopenia in patients with CRPC treated with DEC.     

Second-line chemotherapy with Capecitabine (Xeloda) and Docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial

Purpose

To investigate the efficacy and toxicity of the docetaxel and capecitabine combination in patients with previously treated, unresectable adenocarcinoma of the pancreas.

Patients and Methods

Patients with pancreatic adenocarcinoma, pre-treated with gemcitabine-based chemotherapy, were treated with capecitabine (800?mg/m² orally, twice a day for 14?days) and docetaxel (75?mg/m² i.v, on day1), every 3?weeks. The primary end-point was overall response rate (RR).

Results

Thirty-one patients were enrolled in the study; 93.6% of them had a performance status (PS) of 0?C1 and 96.8% had stage IV disease. Patients received a median of 4 cycles/patient, and the main reason for treatment discontinuation was disease progression. Partial response was observed in three (9.7%) patients, stable disease in seven (22.6%) (disease control rate: 32.3%, 95% CI: 15.80?C48.71%) and disease progression in 21 (67.6%). The median progression-free survival (PFS) was 2.4?months (95% CI: 1.6?C3.13) and the median overall survival (OS) was 6.3?months (95% CI: 3.38?C9.23); the estimated 1-year survival rate was 14.7%. Grade III/IV neutropenia occurred in 10 (32.2%) patients and febrile neutropenia in one patient. Other severe non-hematologic toxicities were mild and manageable. After 2 chemotherapy cycles, pain control occurred in 20% of patients and stabilization of body weight in 40%.

Conclusion

The combination of docetaxel/capecitabine may confer good disease control associated with improvement of quality of life as second-line chemotherapy in patients with metastatic pancreatic cancer.     

Maintenance therapy with pemetrexed versus docetaxel after induction therapy with carboplatin and pemetrexed in chemotherapy-naïve patients with advanced non-squamous non-small-cell lung cancer: a randomized, phase II study

Purpose

The optimal strategy for maintenance chemotherapy is controversial. We evaluated the efficacy and safety of continuation maintenance with pemetrexed and switch maintenance with docetaxel in advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods

Chemotherapy-naïve patients with non-squamous NSCLC were enrolled in this randomized phase II study. Patients who achieved disease control after four cycles of induction therapy with carboplatin (AUC 6) and pemetrexed (500 mg/m²) were randomized to maintenance therapy with pemetrexed (500 mg/m²) or docetaxel (60 mg/m²). The primary endpoint was survival without toxicity, defined as the time from the initiation of maintenance therapy to the first date of any grade 3/4 toxicity or death due to any cause.

Results

A total of eighty-five patients were enrolled in the induction phase, and 26 patients were assigned to the pemetrexed maintenance therapy and 25 patients were assigned to the docetaxel maintenance therapy. Survival without toxicity was significantly longer in the pemetrexed group (median 20.8 months, 95 % confidence interval (CI) 0.7–not estimable) than in the docetaxel group (median 0.5 months, 95 % CI 0.2–2.0, hazard ratio 0.36, 95 % CI 0.17–0.74).

Conclusions

Continuation maintenance with pemetrexed may be a feasible treatment option for patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin and pemetrexed. Switch maintenance with docetaxel may also be efficacious but frequently causes severe hematologic toxicity.     

Phase II study of biweekly docetaxel and S-1 combination chemotherapy as first-line treatment for advanced gastric cancer

Purpose

We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer.

Methods

Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0?C2 and no prior chemotherapy history were eligible for inclusion (n?=?45). Patients received a total of 215 treatment courses (median, 4; range, 2?C12) of S-1 oral administration twice daily for 1?week followed by a drug-free interval of 1?week. Docetaxel (40?mg/m²) was administered intravenously on days 1 and 15.

Results

We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3?months, the median time to progression was 6.9?months, and the median duration of response in 26 patients was 8.0?months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths.

Conclusions

S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.     

The role of βIII-tubulin in non-small cell lung cancer patients treated by taxane-based chemotherapy

Background

The aim of this study is to evaluate whether class III β-tubulin (TUBB3) expression could predict progression-free survival or overall survival in relapsed non-small cell lung cancer (NSCLC) patients treated with taxene-based chemotherapy.

Methods

Immunohistochemistal staining was used to examine the expression of TUBB3 in resected lung tumor specimens obtained from 56 patients treated with platinum-based chemotherapy against recurrent tumors after curative resections. Excision repair cross-complementation group 1, breast cancer susceptibility gene 1, vascular endothelial growth factor, Ki-67, CD34, and p53 were also correlated with clinical features and outcome after treatment.

Results

Of the 56 patients enrolled in the study, 29 were treated by carboplatin plus paclitaxel as first-line treatment, and 24 patients received docetaxel monotherapy as second- or third-line treatment. A positive TUBB3 expression is closely associated with a poor response to taxane-based chemotherapy. TUBB3 expression was an independent prognostic factor for predicting poor progression-free survival after docetaxel administration. However, TUBB3 expression could not predict outcome after carboplatin plus paclitaxel treatment. The other biomarkers tested were not independent prognostic factors for predicting outcome after taxane-based chemotherapy.

Conclusion

TUBB3 expression is associated with resistance to taxane-based chemotherapy and is an independent prognostic factor for predicting poor progression-free survival after docetaxel treatment alone. TUBB3 expression may be a predictive marker for chemoresistance to docetaxel in NSCLC with postoperative recurrent disease.     

Induction chemotherapy with carboplatin and taxol followed by radiotherapy and concurrent weekly carboplatin?+?taxol in locally advanced nasopharyngeal carcinoma

Purpose

Aim of this study was the clinical evaluation of carboplatin?Ctaxol combination in a neoadjuvant and concomitant setting with conventional radiotherapy in loco-regionally advanced nasopharyngeal carcinoma (A-NPC).

Methods

Thirty patients were treated with three cycles of carboplatin (AUC6) plus taxol (175?mg/m²) on day 1 every 3?weeks, followed by weekly carboplatin (AUC1) plus Taxol (60?mg/m2) and concomitant radiotherapy (70?Gy).

Results

We observed the objective complete response rates of 33% (after chemotherapy) and 87% (after chemo-radiotherapy). Treatment tolerability and toxicity were controllable. Three- and five-year progression-free survival were 80 and 75%, respectively, and 3- and 5-year overall survival were 85 and 80% (follow-up 49.5?months). Five-year loco-regional control was 90.3%, and five-year distant metastases?Cfree survival was 85%.

Conclusions

Neoadjuvant chemotherapy with such protocol represents a feasible, efficient treatment for patients with A-NPC, ensuring excellent loco-regional disease control and overall survival with low incidence of distant metastases.     

Salvage chemotherapy for recurrent or persistent clear cell carcinoma of the ovary: a single-institution experience for a series of 20 patients

Background

Recurrent or persistent clear cell carcinoma (CCC) of the ovary is particularly chemotherapy resistant. The purpose of this study was to review our extensive institutional experiences with recurrent or persistent CCC with the aim of finding a more effective chemotherapy regimen.

Methods

The medical records of 67 patients treated for CCC of the ovary were retrospectively reviewed to select patients subsequently treated for recurrence or persistence of the disease.

Results

The review identified 20 patients treated for recurrent or persistent CCC. For these 20 patients, 9 chemotherapeutic regimens, with 125 cycles, were administered. Gemcitabine monotherapy showed the best response rate [1 partial response (20%) and 2 stable diseases out of 5 patients so treated]. A partial response was observed with a combination of docetaxel plus irinotecan in 1 of 11 patients (9%). Stable disease was observed in 1 of 9 cases on a paclitaxel/carboplatin doublet and in 1 case on a docetaxel/carboplatin doublet. The median overall survival time was 8 months (range, 2–52). One group of patients who received gemcitabine therapy showed significantly better survival (n = 5, median 18 months) compared with a group who did not (n = 15, median 7 months) (P = 0.0108, by univariate analysis). In addition, multivariate Cox proportional hazards analysis revealed that gemcitabine administration was a significant factor for survival (hazard ratio: 13.0, 95% CI: 1.4727–115.2255, P = 0.02).

Conclusion

Although most chemotherapeutic regimens for recurrent or persistent CCC have little or no effect, gemcitabine showed modest activity and is the most effective agent we have tested to date.     

A phase II study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin in advanced oesophageal cancer

Background

Concurrent chemoradiotherapy (CRT) is a main treatment option for patients with advanced oesophageal cancer. However, improvement of survival outcomes and toxicities according to the selected treatment is still needed. This phase II trial was conducted to assess the efficacy and safety of concurrent CRT with weekly docetaxel and cisplatin in advanced oesophageal cancer.

Methods

Patients with unresectable oesophageal cancer due to advanced stage or patients medically unfit for surgery were enrolled. Patients received 20?mg/m² docetaxel and 25?mg/m² cisplatin in weeks 1, 2, 3, 5, 6, and 7 with concurrent 54-Gy radiotherapy at 200?cGy/day.

Results

Thirty-six patients with oesophageal squamous cell carcinoma were enrolled from December 2007 to December 2009. Among them, the toxicity and response rate of 35 were evaluated. Thirty-five patients completed radiotherapy as planned, and 33 completed chemotherapy as planned. Grade 3 or 4 toxicity during CRT included leucopenia (5.7?%), febrile neutropenia (2.9?%), oesophagitis (22.9?%), and tracheo-oesophageal fistula (5.7?%). After CRT, 8 patients (22.9?%) had a complete response, 22 (62.9?%) had a partial response, 4 (11.4?%) had stable disease, and 1 (2.9?%) had progressive disease. Improvement of dysphagia was observed in 85.3?%. At a median follow-up of 26.7?months, the median time to progression was 13.5?months, and median overall survival was 26.9?months. The 3-year progression-free survival rate was 16.7?%, and survival rate was 27.8?%.

Conclusion

Concurrent CRT with weekly docetaxel and cisplatin was well tolerated and is a convenient combination with promising efficacy. This result indicated favourable activity in terms of both tumour and symptom control.     

Phase II study of carboplatin and pemetrexed in advanced non-squamous, non-small-cell lung cancer: Kyoto Thoracic Oncology Research Group Trial 0902

Background

Subgroup analyses of randomized studies have consistently shown that pemetrexed is exclusively effective in non-small-cell lung cancer (NSCLC) other than squamous cell carcinoma and the combination of pemetrexed and platinum agents is recommended for first-line chemotherapy in advanced non-squamous NSCLC; however, there have been few prospective studies of a selected population.

Patients and methods

This was a single-arm phase II study of carboplatin and pemetrexed in Japanese patients with chemo-naive advanced non-squamous NSCLC. Patients received six cycles of pemetrexed (500?mg/m²) combined with carboplatin (area under the curve: AUC 6) every 3?weeks. Maintenance chemotherapy with pemetrexed was permitted in patients whose disease did not progress after combination chemotherapy. The primary endpoint was the response rate, and secondary endpoints were safety and survival.

Results

Fifty-one patients were enrolled between November 2009 and March 2011, and 49 patients were evaluable for both safety and efficacy. All but one patient had adenocarcinoma histology. Forty-four (90?%) patients completed four cycles, and 33 (67?%) completed six cycles of chemotherapy. Partial response was achieved in 25 patients (response rate: 51?%) and stable disease in 18 patients (37?%). Median progression-free survival (PFS) and overall survival (OS) were 6.3?months and 24.3?months, respectively. The median PFS and OS were 7.9?months and 24.3?months in patients with epidermal growth factor receptor (EGFR) mutation, and 6.3?months and 21.0?months in patients with EGFR wild type or unknown. There were no statistical differences between EGFR mutants and non-mutants for both PFS (p?=?0.09) and OS (p?=?0.23). Grade 3/4 neutropenia and thrombocytopenia were observed in 16 (33?%) and 9 (18?%) patients, respectively. Non-hematologic toxicities were generally mild, and there were no treatment-related deaths.

Conclusions

The combination of carboplatin and pemetrexed was safe and effective in advanced non-squamous NSCLC. Although the sample size was small, our results indicate that pemetrexed is a key drug for advanced non-squamous NSCLC, irrespective of the EGFR mutation status (UMIN-CTR number 000002451).     

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.     

Phase II study of S-1, a novel oral fluoropyrimidine, and biweekly administration of docetaxel for previously treated advanced non-small-cell lung cancer

Purpose

We examined the safety and efficacy of the combination of S-1 and biweekly docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC).

Methods

Patients with previously treated advanced NSCLC were eligible if they had a performance status of 2 or less, were 80?years or younger, and had adequate organ function. Forty-nine patients (38 men and 11 women; median age, 66?years; range 43?C79?years) were enrolled. Patients were treated with the combination of 80?mg/m² per day of S-1 for 14 consecutive days and 35?mg/m² of docetaxel on days 1 and 15 every 4?weeks.

Results

The overall response rate was 16.3% (95% confidence interval, 7.6?C30.5%). The disease-control rate was 49.0% (95% confidence interval, 34.4?C63.7%). The median survival time after this treatment was 9?months (range 1?C22?months). The median progression-free survival time was 3?months (range 1?C11?months). Response rates and survival times did not differ significantly according to the histological type. Grade 3?C5 toxicities included neutropenia in 51.0% of patients, thrombocytopenia in 2.0%, anemia in 20.4%, infection in 24.5%, anorexia in 12.2%, diarrhea in 14.3%, nausea in 6.1%, and dehydration in 4.2%. There was 1 treatment-related death due to severe anorexia, stomatitis, diarrhea, and, as consequence, dehydration.

Conclusions

The combination of S-1 and biweekly docetaxel is an acceptable therapeutic option in patients with previously treated advanced NSCLC regardless of the histological type.     

Efficacy of weekly paclitaxel in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy

Background

Only partial cross-resistance between docetaxel and paclitaxel has been demonstrated in breast and ovarian cancers. Whether weekly paclitaxel is effective in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy remains unclear, and we aimed to clarify the efficacy and safety of weekly paclitaxel in such patients.

Methods

Patients who had received docetaxel-based regimens were assigned to the prior-docetaxel group, and those who had never received docetaxel were designated as the non-docetaxel group. Paclitaxel at 80?mg/m² was administered by intravenous infusion in all patients, and this was repeated weekly for 3?weeks out of 4.

Results

Between April 2006 and June 2011, 65 patients were studied: 26 in the prior-docetaxel group and 39 patients were non-docetaxel group. The median age, gender, performance status, histological type, history of gastrectomy, and the locations and numbers of metastatic sites did not differ significantly between the two groups. In the prior-docetaxel group, the response rate (RR) was 14.2% (3/21) among patients with measurable lesions, median progression-free survival (PFS) was 79?days [95% confidence interval (CI), 47–135?days], and overall survival (OS) was 123?days (95% CI, 90–215?days) from the initiation of paclitaxel treatment. In the non-docetaxel group, the RR was 11.5% (3/26) among patients with measurable lesions, PFS was 82?days (95% CI, 52–106?days), and OS was 143?days (95% CI, 121–178?days). The efficacy of weekly paclitaxel thus appeared to be similar in the two groups.

Conclusions

Weekly paclitaxel was modestly active in patients with gastric cancer refractory to docetaxel-based chemotherapy.     

Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma

Background

Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods

Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m²/day on day 1), cisplatin (25 mg/m²/day on days 1–3), and 5-fluorouracil (500 mg/m²/day on days 1–3).

Results

The overall response rate to neoadjuvant chemotherapy was 89 %. Three months after the completion of radiotherapy, 53 (93 %) patients achieved complete regression, 3 (5 %) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6–43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3 %, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3 %; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment.

Conclusions

Neoadjuvant–adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC.     

A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer

Background

The aim of this study was to establish the efficacy and safety of doxifluridine and docetaxel for patients with advanced or recurrent gastric cancer.

Methods

The regimen consisted of oral administration of doxifluridine 533 mg/m² per day on days 1–14 and an intravenous infusion of docetaxel 50 mg/m² on day 8. The primary endpoint was the overall response rate. The secondary endpoints were overall survival, progression-free survival, and toxicities.

Results

Between June 2004 and December 2006, a total of 40 eligible patients were enrolled in this study. Seven of them showed a partial response, with an overall response rate of 17.5%. The response rate was 18.8% in 32 patients with refractory tumors. The median progression-free survival time and the median overall survival time were 2.6 months and 12.7 months, respectively, in all 40 patients; and 2.6 months and 14.0 months, respectively, in the 32 patients with refractory tumors. Grade 3/4 hematological toxicity included neutropenia in 52.5%, leukocytopenia in 17.5%, and febrile neutropenia in 7.5%. Grade 3 or more nonhematological toxicities were infrequent.

Conclusion

The combination chemotherapy of doxifluridine and docetaxel was well tolerated and relatively effective when used as a second-line chemotherapy for advanced or recurrent gastric cancer.     

A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma

Purpose

Studies treating adenocarcinoma of the pancreas with gemcitabine alone or in combination with a doublet have demonstrated modest improvements in survival. Recent reports have suggested that using the triple-drug regimen FOLFIRINOX can substantially extend survival in patients with metastatic disease. We were interested in determining the clinical benefit of another three-drug regimen of gemcitabine, docetaxel and capecitabine (GTX) in patients with advanced pancreatic adenocarcinoma.

Patients and methods

The cases of 154 patients, who received treatment with GTX chemotherapy with histologically confirmed locally advanced or metastatic pancreatic adenocarcinoma, were retrospectively reviewed. All demographic and clinical data were captured including prior therapy, adverse events, treatment response and survival.

Results

One hundred and seventeen metastatic and 37 locally advanced cases of adenocarcinoma of the pancreas were reviewed. Partial responses were noted in 11% of cases, and stable disease was observed in 62% of patients. Responses significantly correlated with toxicity (neutropenia, ALT elevation and hospitalizations). Grade 3 or greater hematologic and non-hematologic toxicities were noted in 41% and 9% of cases, respectively. Overall median survival was 11.6?months. Chemotherapy na?ve patients with metastatic and locally advanced disease achieved a median survival of 11.3 and 25.0?months, respectively.

Conclusions

We observe a substantial survival benefit with GTX chemotherapy in our cohort of patients with advanced pancreatic cancer. These findings warrant further investigation of this combination in this patient population.     

Phase II study of docetaxel,cisplatin, and concurrent radiation followed by platinum-based adjuvant chemotherapy for technically unresectable,locally advanced head and neck squamous cell carcinoma

Background

Phase I study of weekly administration of low-dose docetaxel/cisplatin concurrent with conventionally fractionated radiotherapy for locally advanced head and neck squamous cell carcinoma suggested the recommended dose of docetaxel at 10 mg/m² and cisplatin at 20 mg/m². Phase II study of the concurrent chemoradiotherapy for technically resectable disease showed satisfactory results.

Methods

This phase II study was designed to address efficacy and safety when patients with technically unresectable disease were treated with concurrent chemoradiotherapy, followed by two cycles of moderate-dose platinum-based adjuvant chemotherapy: docetaxel, cisplatin, and fluorouracil (modified TPF). Modified TPF was replaced with docetaxel/carboplatin when renal impairment became evident. Surgical salvage was considered when residual or recurrent locoregional disease was technically resectable and free of distant metastasis.

Results

Of 33 enrolled patients, 31 were analyzable: 24 (78 %) and 18 (58 %) patients completed chemoradiotherapy and adjuvant chemotherapy, respectively; 15 (48 %) patients completed study treatment per protocol, and overall complete response rate was 45 %. Seven patients underwent surgical salvage, which was successful in 4 patients. At a median follow-up of 60.8 months for surviving patients, median progression-free survival and median overall survival were 16.2 and 39.9 months, respectively. Grade 3 or 4 toxicity included mucositis (77 %) and dysphagia (45 %) during the chemoradiotherapy period and neutropenia (100 %) and febrile neutropenia (35 %) during the adjuvant period. No patient died of toxicity.

Conclusion

The tested regimen seems effective, although there is room for improvement in adjuvant chemotherapy because of the high toxicity and low compliance of modified TPF.