A phase II study of modified dose-dense paclitaxel and every 4-week carboplatin for the treatment of advanced-stage primary epithelial ovarian, fallopian tube, or peritoneal carcinoma

Purpose

Traditional dose-dense chemotherapy regimens for advanced stage ovarian cancer incorporate weekly paclitaxel on a 21-day cycle and are associated with favorable efficacy but high rates of neutropenia, thrombocytopenia, and anemia. The purpose of this phase II study was to assess the response rate and toxicity of modified dose-dense paclitaxel and every 4-week carboplatin for the treatment of advanced-stage ovarian, fallopian tube, and primary peritoneal carcinoma.

Methods

All eligible patients were treated with 6 cycles of intravenous dose-dense paclitaxel (80 mg/m²) days 1, 8, and 15 and carboplatin (AUC 5 or 6) Day 1 during a 28-day cycle in accordance with an IRB-approved protocol. Patients who had clinically defined stable disease or better with a CA-125 ≤ 35 U/ml following the completion of primary induction therapy were subsequently administered a planned 12 cycles of paclitaxel (135 mg/m²; every 21 days) consolidation therapy.

Results

Eighty-eight patients received at least 3 cycles of induction dose-dense chemotherapy, of whom 76 completed 6 cycles of chemotherapy; the overall response rate was 84.2 % (56.6 % complete response). Fifty-three patients received an aggregate 473 cycles (median = 9; range 1–12) of consolidation chemotherapy. Grade 3–4 hematological toxicity included neutropenia (22.7 %), thrombocytopenia (7.9 %), and anemia (1.1 %). Further, grade 3 neuropathy developed in one (1.1 %) patient. The patients’ median disease-free survival and overall survival were 22.5 and 31.5 months, respectively.

Conclusions

This phase II study suggests that first-line treatment comprising modified dose-dense paclitaxel and monthly carboplatin chemotherapy with paclitaxel consolidation therapy preserves the efficacy of traditional dose-dense chemotherapy, while minimizing hematologic toxicity.     

Safety and efficacy of sequential chemotherapy with carboplatin plus gemcitabine followed by weekly paclitaxel in advanced non-small cell lung cancer

Background

Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC.

Methods

Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m² (days 1 and 8) every 3 weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80 mg/m².

Results

In total, 46 patients were included. Median age was 59.6 years (range 41.3–74.3 years) and 93.5 % (n = 43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3 %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of carboplatin–gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49 %. Sixteen (37 %) patients had a response to carboplatin–gemcitabine, increasing to 21 (49 %) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin–gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin–gemcitabine, 4 (21 %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped because of toxicity.

Conclusion

Sequential chemotherapy with carboplatin–gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients.     

A phase II trial of concurrent chemoradiotherapy with weekly paclitaxel and carboplatin in advanced oesophageal carcinoma

Background

This study was performed to assess the efficacy and feasibility of definitive chemoradiotherapy consisting of weekly doses of combined paclitaxel and carboplatin concurrent with radiation therapy, followed by 2 cycles of consolidation chemotherapy for advanced esophageal carcinoma.

Methods

Eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; Eastern Cooperative Oncology Group (ECOG) score ≤ 2; and adequate organ function. Patients received concurrent chemoradiation therapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m²) and carboplatin (area under the curve, AUC = 2) on days 1, 8, 15, 22 and 29. The two-cycle consolidation chemotherapy protocol was paclitaxel (175 mg/m²) plus carboplatin (AUC = 5) administered on days 57 and 85, after concurrent chemoradiotherapy.

Results

Between August 2013 and February 2015, 65 patients with oesophageal carcinoma were enrolled in the study; 34 (52.3%) were newly diagnosed and 31 (47.6%) had postoperative local regional lymph node metastasis. The median overall survival time was 21.7 months (95% confidence interval [CI] 16.7–26.6), and the median progression-free survival time was 12.1 months (95% CI 9.0–15.3). A total of 96.9% (63/65) and 67.6% (44/65) patients completed ≥5 cycles and all 7 cycles of chemotherapy, respectively. A total of 93.8% (61/65) patients completed radiation therapy. The 1- and 2-year overall survival rates were 73.7 and 42.0%, respectively. The 1- and 2-year progression-free survival rates were 50.6 and 31.1%, respectively. Grade 3–4 toxicity during chemoradiotherapy included neutropenia (24.5%), thrombocytopenia (4.6%), fatigue (1.5%), anaemia (1.5%), radiation dermatitis (1.5%), pneumonitis (1.5%), oesophagitis (4.6%) and vomiting (1.5%).

Conclusions

In patients with locally advanced oesophageal cancer, the combination of weekly doses of paclitaxel and carboplatin was well tolerated and produced comparable results. A three-arm randomised phase III trial (NCT02459457) comparing paclitaxel in combination with cisplatin, carboplatin or 5-fluorouracil with concurrent radiotherapy is on-going at our hospital.

     

Phase II study of docetaxel and vinorelbine as adjuvant chemotherapy for resected non-small cell lung cancers

Purpose

For patients with resected stage II–III non-small cell lung cancers (NSCLCs), adjuvant cisplatin-based chemotherapy improves survival over surgery alone. For cisplatin ineligible patients, there is no standard adjuvant option. We evaluated drug delivery and toxicity of docetaxel and vinorelbine in patients who could not receive cisplatin.

Methods

Patients with completely resected stage IB–III NSCLCs were treated with up to 4 cycles of docetaxel and vinorelbine at the recommended phase II dose. The primary endpoint was drug delivery compared to historical delivery of adjuvant cisplatin plus vinorelbine. Secondary endpoints were toxicity and feasibility.

Results

Twenty-five patients were enrolled. Overall, 13/25 (52 %, 95 % CI 34–70) completed 4 cycles, and 19/25 (76 %, 95 % CI 60–87) completed ≥3 cycles. Twenty of 25 patients (80 %) experienced a Grade 3 or 4 adverse event.

Conclusions

Delivery of this dose and schedule of docetaxel and vinorelbine was difficult with a dose delivery comparable to cisplatin plus vinorelbine, and cisplatin plus docetaxel, used in this setting.     

不能手术的Ⅲ期非小细胞肺癌患者每周紫杉醇和卡铂并同步放疗的诱导化疗:一个Ⅱ期研究结果(英文)

Objective: several trials have suggested the superiority of concurrent chemoradiotherapy. It has been hypothesized that the addition of systemic dose sequential chemotherapy to concurrent chemoradiotherapy, as induction or as consolidation, might further improve survival rates. So we sought to evaluate the safety and efficacy of induction paclitaxel and carboplatin followed by weekly paclitaxel and carboplatin with concurrent radiotherapy in inoperable stage Ⅲ non-small cell lung cancer (NSCLC). Methods: Fifty-six patients with stage Ⅲ inoperable NSCLC received induction chemotherapy with 2 cycles of paclitaxel 200 mg/m2 and carboplatin AUC-6 every 3 weeks then patients were assigned to concurrent chemoradiotherapy with paclitaxel 45 mg/m2 and carboplatin AUC-2 weekly along with concurrent radiotherapy at dose of 60 Gy (1.8 Gy/d x 5 d/week). Results: Median age of the 56 eligible patients was 61 years, most of them were males (87.5%). Squamous cell carcinoma was the most common pathological type (55.4%) and 85.7% had a performance status of 1. The majority of patients were presented with stage ⅢB (62.5%). Neutropenia was the most common toxicity during induction therapy (12.5% expressed grade 3) whereas esophagitis was the most common non hematologic adverse reaction during concurrent chemoradiotherapy (14.3% of grade 3). The overall response rate was 71.6% with complete response in 19.6%. After median follow up of 20 months, the median survival time was 13 months (95% CI: 10.917-15.083) and 1 year overall survival rate was 53.6%. Conclusion: This regimen has demonstrated an acceptable toxicity profile and encouraging response to treatment. Evaluation of this regimen in larger number and a phase Ⅲ trial are recommended.     

Phase II study of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer

Purpose

This phase II study is performed to evaluate the safety, efficacy and tolerability of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer (NSCLC).

Patients and methods

All patients were treated with the combination of docetaxel 35 mg/m² by IV infusion over 30–60 min weekly, on days 1, 8, and 15, for 3 weeks followed by 1 week of rest, with intravenous carboplatin (AUC 6) administered immediately afterward on day 1. Cycles were repeated every 28 days.

Results

Forty-seven (95.9%) of the 49 patients were assessable for response, one case of complete response and 17 cases of partial response were confirmed, giving an overall response rate of 36.7% (95% CI 23.2–50.2%). The median time to progression and overall survival (OS) for all patients were 5.2 months (95% CI 4.1–6.3 months) and 10.4 months (95% CI 7.3–13.5 months), respectively. The estimate of OS at 12 months was 37.6% (95% CI 24.0–51.2%). The most severe hematologic adverse event was anemia, which occurred with grade 3/4 intensity in 7 (14.9%) patients. Neutropenia occurred with grade 3 intensity in 4 (8.5%) patients. However, no grade 4 neutropenia was observed. Grade 3 nausea/vomiting, diarrhea, asthenia, nail changes, and skin reaction were observed in 6 (12.8%), 3 (6.4%), 2 (4.3%), 2 (4.3%) and 1 (2.1%) patients. Yet, no grade 4 non-hematologic toxicity was observed.

Conclusions

The combination of carboplatin with weekly docetaxel is a tolerated treatment modality with encouraging activity and survival outcome in previously untreated patients with advanced NSCLC.     

The safety and efficacy of paclitaxel and carboplatin with or without bevacizumab for treating patients with advanced nonsquamous non-small cell lung cancer with interstitial lung disease

Purpose

Optimal chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) with interstitial lung disease (ILD) is established for paclitaxel and carboplatin, but is otherwise controversial. Therefore, we assessed the efficacy and safety of paclitaxel and carboplatin with or without bevacizumab for treating these patients.

Methods

We analyzed the outcomes of 21 patients with advanced nonsquamous NSCLC with ILD who received paclitaxel and carboplatin without (paclitaxel–carboplatin group; n = 11) or with bevacizumab (paclitaxel–carboplatin–bevacizumab group; n = 10) between April 2008 and October 2013.

Results

The median progression-free survival time of the paclitaxel–carboplatin–bevacizumab group was 5.3 months (95 % CI 0.4–11.6 months) compared with 4.4 months (95 % CI 0.9–6.3 months) for the paclitaxel–carboplatin group (p = 0.060). Their respective median overall survival times were 16.1 months (range 0.4–34.8 months) and 9.7 months (range 2.6–37.0 months) (p = 0.772) with corresponding overall response rates of 40 and 27 % (p = 0.659), respectively. One patient in the paclitaxel–carboplatin–bevacizumab group experienced chemotherapy-related exacerbation of ILD (0/11 vs. 1/10; p = 0.476).

Conclusions

The addition of bevacizumab to paclitaxel and carboplatin may provide an effective and safe treatment option for patients with advanced nonsquamous NSCLC with ILD.     

Phase II study of weekly carboplatin and irinotecan as first-line chemotherapy for patients with advanced non-small cell lung cancer

Purpose

Platinum-based doublet chemotherapy has a major role in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The weekly fractionated administration of cisplatin for patients with NSCLC has been shown to be active. Irinotecan and carboplatin are effective against NSCLC and demonstrated synergism with non-cross-resistance in preclinical studies. We conducted a phase II study of weekly combination of carboplatin and irinotecan as first-line chemotherapy for patients with advanced NSCLC.

Methods

From March 2009 to November 2011, 24 patients who were diagnosed with inoperable or metastatic NSCLC were enrolled. Treatment consisted of carboplatin at an AUC 2.5 mg/mL/min over 30-min intravenous infusion and irinotecan 65 mg/m² over 90-min intravenous infusion on day 1 and day 8, respectively. The treatment was repeated every 3 weeks.

Results

One patient (4.2 %) achieved complete response, and seven (29.2 %) showed partial response. Overall response rate was 33.3 %, with median response duration of 4.55 months. Nine patients had stable disease, and disease control rate was 70.8 %. With median follow-up of 12.8 months, median progression-free survival was 4.5 months (95 % CI 1.8–7.2), and median overall survival was 15.5 months (95 % CI 6.9–24.1). Major toxicity was myelosuppression. Grade 3–4 neutropenia and thrombocytopenia occurred in 50 and 20.8 % of patients, respectively. Two patients experienced febrile neutropenia. Non-hematologic toxicities were generally mild. One patient suffered grade 4 diarrhea, and one treatment-related death due to pneumonia was occurred.

Conclusion

The weekly combination of carboplatin and irinotecan showed favorable activity and manageable toxicity profiles in chemo-naïve patients with advanced NSCLC. Our results suggest that this regimen can be a reasonable chemotherapeutic option for patients with advanced NSCLC.     

Phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer

We conducted a phase II trial to investigate the efficacy of concurrent chemoradiation in patients with stage III non-small-cell lung cancer (NSCLC). Thirty patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Patients received six weekly cycles of paclitaxel 45 mg/m(2) over 1 h; carboplatin at (area under the curve) AUC 2; and radiation therapy of 60 Gy. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy over 4 weeks) followed by a boost to the primary tumor (20 Gy in 2 weeks). After the initial phase of concurrent chemoradiation, patients received an additional four cycles of paclitaxel 175 mg/m(2) over 3 h and carboplatin at AUC 6 every 3 weeks. The overall objective response rate of 30 assessable patients was 76.7%. At the median follow-up time of 13.1 months, the median survival time was 14.5 months (95% CI, 10.59-18.48). The median progression-free survival was 10.5 months (95% CI, 7.72-13.28). The major toxicity was hematologic. The incidence of grade 3 esophagitis was 10%. In conclusion, this chemoradiation regimen is well tolerated and shows significant clinical results for locally advanced NSCLC. Locoregional failure rate remains an important issue with this newer chemotherapeutic regimen. A novel chemotherapy and radiation therapy is clearly needed.     

Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy

Background

We have previously reported the superior feasibility and safety of adjuvant S-1 plus docetaxel in patients with stage III gastric cancer during a prospective phase II study. We report 3-year follow-up data on patients enrolled in this study.

Patients and methods

Fifty-three patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled into this study. They received oral S-1 (80 mg/m²/day) for 2 consecutive weeks and intravenous docetaxel (40 mg/m²) on day 1, repeated every 3 weeks (one cycle). Treatment was initiated within 45 days after surgery and repeated for four cycles, followed by S-1 monotherapy (4 weeks on, 2 weeks off) until 1 year after surgery. Three-year overall survival (OS) and disease-free survival (DFS) were evaluated.

Results

The OS rate at 3 years was 78.4 % [95 % confidence interval (CI), 67.9–90.6 %] and the DFS rate at 3 years was 66.2 % (95 % CI, 54.4–80.7 %). Subgroup analyses according to disease stage showed a 3-year OS and DFS rate of 85.7 % (95 % CI, 74.9–98.1 %) and 70.8 % (95 % CI, 57.1–87.8 %) for stage IIIA, and 62.5 % (95 % CI, 42.8–91.4 %) and 56.2 % (95 % CI, 36.5–86.7 %) for stage IIIB, respectively.

Conclusions

On the basis of 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel yielded promising OS and DFS in stage IIIA gastric cancer patients who had undergone D2 gastrectomy. We believe that this regimen is a candidate for future phase III trials studying the optimal adjuvant chemotherapy regimen for stage III gastric cancer.     

Phase II study of single agent oral vinorelbine as first-line treatment in patients with HER-2 negative metastatic breast cancer

Purpose

Previous studies indicated that oral chemotherapy is convenient and preferred by many patients. We hereby report the efficacy and safety of oral vinorelbine as first-line chemotherapy for metastatic breast cancer (MBC).

Methods

Thirty-one patients with HER-2 negative MBC were enrolled between January 2007 and December 2010 in a prospective phase II trial. Patients were treated every 3 weeks with oral vinorelbine 60 mg/m² Days 1 and 8 for the 1st cycle and thereafter 80 mg/m² Days 1 and 8 every 3 weeks. Treatment was administered until disease progression or unexpected adverse event or patient refusal to continue. Primary endpoint was objective response rate (ORR); secondary endpoints were time-to-progression (TTP), overall survival (OS) and safety. Follow-up results until October 2012 are reported.

Results

Median age was 42 years (range 33–75). 26 (84 %) patients had 2 or more metastatic sites. A median of 6 cycles were administered (range 2–20). ORR was achieved in 9 (29 %) patients including 1 complete and 8 partial responses. 12 (39 %) patients had stable disease, resulting in a disease control rate of 68 %. Median TTP was 5.2 months [95 % CI 2.8–7.5]. Median OS was 16 months [95 % CI 11.3–20.7]. 3 (10 %) patients developed Grade 3–4 neutropenia. No events of febrile neutropenia, cardiac, renal toxicities or alopecia were recorded. Grade 3 thrombocytopenia and nausea-vomiting were reported in 2 (6 %) and 5 (16 %) patients, respectively.

Conclusion

Results show a good efficacy and tolerance profile of oral vinorelbine as first-line chemotherapy for HER-2 negative MBC patients.     

A Multicenter Randomized Controlled Study of Paclitaxel plus Carboplatin versus Oral Uracil-Tegafur as the Adjuvant Chemotherapy in Resected Non–Small Cell Lung Cancer

Introduction

We conducted a randomized controlled study to compare the survival benefit of paclitaxel plus carboplatin and oral uracil-tegafur (UFT) as adjuvant chemotherapy in resected NSCLC.

All-oral combination of vinorelbine and capecitabine as first-line treatment in HER2/Neu-negative metastatic breast cancer

Purpose

To evaluate the efficacy and safety of an all-oral vinorelbine and capecitabine combination therapy in anthracycline- ± taxane-pretreated HER2/Neu-negative metastatic breast cancer (MBC).

Methods

A phase 2 trial including women >18 years with HER2/Neu-negative MBC previously exposed to anthracycline- ± taxane-based chemotherapy in the adjuvant or neoadjuvant setting. Enrolled patients received oral vinorelbine 60 mg/m² on days 1 and 8 and oral capecitabine 1,000 mg/m² twice daily on days 1–14 on a 3 weekly schedule. Patients with progressive disease after 3 cycles discontinued the study, while the remaining patients continued treatment for a maximum of 6 cycles.

Results

From January 2007 to March 2011, 30 patients were enrolled in this study (median age 47 years). In the 28 evaluable patients, the overall response rate was 57.1 % (95 % CI 30–67 %), including 3 complete (10.7 %) and 13 partial (46.4 %) responses. Six (21.4 %) patients suffered from disease progression. With a median follow-up time of 13 months, the median time to disease progression was 8.6 months (95 % CI 6.2–10.6 months) and the median survival time was 27.2 months. Treatment-related adverse events were manageable, and no World Health Organization grade 4 toxicities were noted. Neutropenia observed in 6 (21.4 %) patients was the main grade 3 toxicity. Grade 3 nausea and vomiting were reported in 2 (7.1 %) and 3 (10.7 %) patients, respectively. Two (7.1 %) patients developed grade 3 hand and foot syndrome.

Conclusion

These results show that the combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for HER2/Neu-negative MBC patients pretreated with anthracyclines ± taxanes.     

A phase 1 study of linifanib in combination with carboplatin/paclitaxel as first-line treatment of Japanese patients with advanced or metastatic non-small cell lung cancer (NSCLC)

Introduction

Linifanib is a potent, orally active, and selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor kinase activities with clinical efficacy in non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study evaluated the pharmacokinetics, safety, and efficacy of linifanib in combination with carboplatin/paclitaxel in Japanese patients with advanced NSCLC.

Methods

Carboplatin (AUC = 6 mg/mL/min) and paclitaxel (200 mg/m²) were administered on day 1 of each 21-day cycle up to a maximum of six cycles. Oral linifanib (7.5 mg) was given to six patients once daily throughout all cycles and escalated to 12.5 mg/day in a second cohort of six patients.

Results

Twelve patients received at least one dose of linifanib. The most common adverse events were hematologic and consistent with expected toxicities with carboplatin/paclitaxel. With 12.5 mg linifanib, grade 3/4 neutropenia, leukopenia, and thrombocytopenia occurred in 100, 83, and 83 % of patients, respectively. Dose-limiting grade 4 thrombocytopenia occurred in one patient at each dose level. Linifanib pharmacokinetics was similar to that in non-Japanese patients. At 12.5 mg, linifanib C _max was 0.32 μg/mL and AUC₂₄ was 4.29 μg h/mL. Linifanib C _max occurred at 2–3 h with both doses and when given alone or in combination with carboplatin/paclitaxel. Exposure to linifanib appeared to be increased by carboplatin/paclitaxel, and exposure to paclitaxel appeared to be increased by linifanib. Partial responses were observed in nine patients.

Conclusions

Linifanib added to carboplatin/paclitaxel is well tolerated in Japanese patients with advanced/metastatic NSCLC. The recommended dose of linifanib with carboplatin/paclitaxel is 12.5 mg, same as for US patients.     

Phase I dose-escalating study of 24-h continuous infusion of 5-fluorouracil in combination with weekly docetaxel and cisplatin in patients with advanced gastric cancer

Purpose

To determine the maximum-tolerated dose (MTD) of a 24-h continuous infusion of 5-fluorouracil (5-FU) when administered in combination with a fixed weekly dose of docetaxel and cisplatin in patients with advanced gastric cancer.

Methods

Patients with advanced gastric adenocarcinoma (n = 21) received a weekly regimen of docetaxel, cisplatin and 5-FU (DCF) for 3 consecutive weeks every 4 weeks. The doses of docetaxel and cisplatin were fixed at 33.3 and 30 mg/m², respectively. The dose of 5-FU was increased from a starting dose of 1,000 mg/m² to the MTD.

Results

A total of 53 cycles of chemotherapy were administered (median = 3 cycles/patient). The MTD of 5-FU was 1,750 mg/m². All 21 patients were assessed for toxicity and 19 patients (90%) were evaluated for response. Both grade 3–4 hematologic and non-hematologic toxicities occurred in less than 10% of patients and there were no treatment-related deaths. Among the 19 patients, we observed 1 complete and 4 partial responses for an overall response rate of 26% (95% CI: 6–46%). This rate increased to 39% (95% CI: 12–66%) in 13 chemotherapy-naïve patients.

Conclusions

A consecutive weekly DCF regimen at 4-week intervals appears feasible for advanced gastric cancer with a favorable toxicity profile. The recommended doses are 33.3 mg/m² of docetaxel, 30 mg/m² of cisplatin and 1,500 mg/m² of a 24-h continuous intravenous infusion of 5-FU. The response of this weekly regimen in our study was favorable and deserved further investigation in a phase II trial.     

Phase II study of carboplatin and gemcitabine as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer: a report from the Central Japan Lung Study Group, CJLSG 0503 trial

Background

The aim of this phase II study was to evaluate the feasibility and safety of a carboplatin and gemcitabine combination regimen in the treatment of completely resected non-small cell lung cancer (NSCLC).

Methods

Patients with completely resected pathologically documented stage IB, II or IIIA NSCLC were treated with carboplatin and gemcitabine. Chemotherapy consisted of 4 cycles of carboplatin at an area under the curve of 5 (level 1) or 4 (level 2) on day 1 combined with gemcitabine 1,000 mg/m² on days 1 and 8 every 3 weeks. The primary endpoint of this study was the completion rate of 4 cycles.

Results

Twenty patients were treated, and the patient’s demographics were: median age 61 years (range 51–74), gender male (n = 13, 65%)/female (n = 7, 35%), stage IB (n = 8, 40%), IIA (n = 1, 5%), IIB (n = 6, 30%), IIIA (n = 5, 25%). Seventeen patients (85%, 95% confidence interval 64.0–94.8) received the planned 4 cycles of the chemotherapy regimen at level 1 every 3 weeks. Among the 3 patients who failed to complete 4 cycles, the reasons for stopping were refusal (n = 1), thrombocytopenia (n = 1) and rash (n = 1). The main adverse effects were hematological toxicity as well as grade 3/4 neutropenia and thrombocytopenia (which occurred in 65% and 40% of the patients, respectively).

Conclusions

Adjuvant chemotherapy with a carboplatin and gemcitabine combination regimen has an acceptable toxicity profile, and the majority of patients completed 4 cycles of therapy.     

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.     

Weekly docetaxel in patients with platinum-refractory metastatic or recurrent squamous cell carcinoma of the head and neck

Background

The objective of the study was to investigate the efficacy and tolerability of weekly docetaxel in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Methods

Patients fulfilling the following criteria were enrolled: histologically confirmed SCCHN; documented progressive disease (PD) after platinum-based treatment; Eastern Cooperative Oncology Group (ECOG) 0–2; measurable disease; not candidates for local therapy. Docetaxel (35 mg/m²) was administered for 3 weeks, every 4 weeks for a maximum of 6 cycles.

Results

A total of 23 patients were treated. All patients were assessable for toxicity and response. The overall response rate was 13.0% (3/23) and disease control rate was 34.7% (8/23). Median progression-free and overall survival (OS) was 9 (95% CI, 7.6–10.4 weeks) and 29 weeks (95% CI, 10.8–47.1 weeks), respectively. Most common hematological toxicities were grade 1–2 anemia (6/23, 26.1%) and nonhematological toxicities were mild and manageable. There was no treatment-related death.

Conclusion

Weekly docetaxel regimen had good clinical activity with an acceptable toxicity in patients with platinum-refractory SCCHN.     

A prospective phase II trial of S-1 and cisplatin-based chemoradiotherapy for locoregionally advanced esophageal cancer

Purpose

S-1 is a novel oral fluoropyrimidine anticancer agent designed to enhance clinical efficacy, reduce gastrointestinal toxicity, and enhance radiotherapy effectiveness. A phase II trial was conducted to evaluate the efficacy and safety of preoperative chemoradiation with S-1 and cisplatin in locoregionally advanced esophageal cancer.

Methods

Eligible patients had stage IIA-IVA esophageal cancer. Patients received two cycles of S-1 (days 1–14 and days 22–35) and cisplatin (days 1 and 22) with concurrent radiotherapy (50.4 Gy total; 1.8 Gy/fraction). Esophagectomy was performed between weeks 12 and 18 as determined by the specialist multidisciplinary team.

Results

Sixty patients were enrolled in this study between March 2008 and August 2011, and 59 were eligible. The clinical stage was ≥T3 in 28 patients (47 %) and N1 in 43 patients (72 %), with squamous cell carcinoma histology in 58 patients (97 %). Fifty-four patients (90 %) completed the planned chemoradiation. After chemoradiation, the clinical tumor response rate was 64.4 %. The primary toxicities included neutropenia (24 %) and esophagitis (8.5 %). Three treatment-related deaths were noted. Twenty-five patients (42 %) underwent esophagectomy following chemoradiation, and 15 achieved complete pathologic regression. The estimated overall survival and progression-free survival rates after 2 years were 65 and 48 %, respectively.

Conclusions

Concurrent chemoradiation with S-1 and cisplatin exhibited encouraging results with complete pathologic regression. The survival data were promising compared with the historical data of 5FU/cisplatin and should be confirmed in a randomized phase III trial. Toxicities were significant but clinically manageable.     

Combination of gemcitabine and carboplatin as first line treatment in elderly patients or those unfit for cisplatin-based chemotherapy with advanced transitional cell carcinoma of the urinary tract

Purpose

Although cisplatin-based chemotherapy is the standard of care for advanced transitional cell carcinoma, tolerability is a challenging issue in unfit patients. This study was conducted to evaluate the efficacy, toxicity, and tolerability of the combination of gemcitabine and carboplatin in unfit patients with advanced transitional cell carcinoma.

Methods

Thirty-one patients who had advanced transitional cell carcinoma and one of the following clinical features were evaluated: Eastern Cooperative Oncology Group performance status equal or greater than 2, age older the 75 years or estimated glomerular filtration rate less than 60 ml/min. The patients were treated with carboplatin and gemcitabine delivered every 4 weeks.

Results

Of the 31 patients, 71 % had an estimated glomerular filtration rate of less than 60 ml/min, and the remaining patients were treated by this protocol due to poor performance status or age older than 75. The median age of the patients was 74 years old. A total of 162 cycles of treatment were delivered to the patients. The overall response rate was 45.1 %. After the median follow-up of 15 months, the median progression-free survival time was 9.4 months (95 % CI 7.3–11.4) and overall survival time was 20 months (95 % CI 14.9–25.0). Grades 3 and 4 anemia, thrombocytopenia, and neutropenia were observed in 22.6, 6.45, and 6.45 % of patients, respectively. There was no treatment-related mortality in our patient series.

Conclusion

The combination of gemcitabine and carboplatin is effective in elderly patients with advanced transitional cell carcinoma or those unfit for cisplatin-based chemotherapy, with manageable toxicity.