Promising overall survival of patients with recurrent/metastatic squamous cell carcinoma of head and neck receiving gemcitabine plus cisplatin treatment: report of a multi-center phase II study

Purpose

The efficacy and safety of gemcitabine in combination with cisplatin (GC) as the first-line treatment in patients with recurrent/metastatic (R/M) squamous cell carcinoma of head and neck (SCCHN) was examined.

Patients and methods

Patients with R/M SCCHN without prior treatment for their R/M disease were eligible and treated with gemcitabine 1,250 mg/m² on day 1, day 8 and cisplatin 80 mg/m² on day 8 every 21 days.

Results

Forty patients were enrolled from March 2004 to January 2006, and 30 were evaluable for treatment effectiveness and outcome. The median age of evaluable patients was 50 years and all patients were male. Partial response was observed in 9 (30%) and stable disease in 7 (23.3%) patients. The overall response rate and disease control rate was 30 and 53.3%, respectively. The major toxic effects were ≥grade 3 leukopenia and anemia (65 and 27.5%, respectively). With a follow-up of 72 months, the median time to progression (TTP) was 128 days (95% CI, 78–242) and median overall survival (OS) was 401 days (95% CI, 216 ~not reached).

Conclusions

This GC regimen demonstrates a good activity and a promising survival period in patients with R/M SCCHN.     

Preoperative treatment with bevacizumab in combination with chemotherapy in patients with unresectable metastatic colorectal carcinoma

Purpose

This prospective observational study assessed the efficacy of bevacizumab in combination with chemotherapy as preoperative treatment to downsize tumours for radical resection in patients with unresectable metastatic colorectal cancer (mCRC).

Patients/methods

Patients with mCRC initially unresectable according to predefined criteria were included. Preoperative treatment consisted of bevacizumab (5 mg/kg) combined with oxaliplatin- or irinotecan-based chemotherapy, which was followed by surgery in patients showing clinical benefit. Resection rate was the primary endpoint. Response rate (RR) and clinical benefit of preoperative chemotherapy, and overall survival (OS) were secondary endpoints.

Results

A total of 120 eligible patients were included and received preoperative treatment. Chemotherapy was irinotecan-based in 73 (61 %) patients, oxaliplatin-based in 25 (21 %) and 22 (18 %) patients received more than one line. A RR of 30 % and a clinical benefit rate of 73 % were observed with preoperative chemotherapy. Metastatic resection was possible in 61 (51 %) patients. Median OS was 33 months (95 % CI 31–NA months) for patients undergoing surgery, and 15 months (95 % CI 11–25 months) in non-operated patients. Thirty-five patients experienced 59 postoperative complications (morbidity rate 57 %).

Conclusion

Preoperative bevacizumab-based chemotherapy offers a high surgical rescue rate in patients with initially unresectable mCRC.     

Correlation between overall survival and other endpoints in clinical trials of second-line chemotherapy for patients with advanced gastric cancer

Background

The correlation between progression-free survival (PFS) or time to progression (TTP) and overall survival (OS) has been evaluated in patients with advanced gastric cancer (AGC) who received first-line chemotherapy. No corresponding analysis has been done in patients who have undergone second-line chemotherapy.

Methods

We evaluated the correlation between PFS, TTP, objective response rate (ORR), disease control rate (DCR), and OS in patients with AGC who underwent second-line chemotherapy. Correlations were evaluated by Spearman rank correlation coefficient (ρ).

Results

Sixty-four trials, including 10 randomized studies, were selected for analysis. Median PFS/TTP moderately correlated with OS (ρ = 0.56). The correlation tended to be stronger in non-Asian trials (ρ = 0.74) than in Asian trials (ρ = 0.37). ORR and DCR did not strongly correlate with OS (ρ = 0.38 for ORR; ρ = 0.54 for DCR). The hazard ratio of PFS and OS in each of the arms of the 10 randomized studies also showed a low correlation (ρ = 0.36).

Conclusions

PFS/TTP, ORR, and DCR did not correlate sufficiently with OS to be used as surrogate endpoints in patients with AGC who have undergone second-line chemotherapy. Further research is needed based on individual patient data from ongoing randomized trials.     

Triplet combination with paclitaxel, cisplatin and 5-FU is effective in metastatic and/or recurrent nasopharyngeal carcinoma

Purpose

Platinum-based chemotherapy is the recognized first-line treatment for metastatic nasopharyngeal carcinoma (NPC). However, no standard treatment regimens have been established. This phase II study was designed to evaluate the efficacy and safety of a paclitaxel, cisplatin and 5-FU combination in metastatic and/or recurrent NPC.

Methods

Patients with evaluable metastatic and/or recurrent NPC were entered into this study. Treatment consisted of paclitaxel at a dose of 135 mg/m² on day 1, cisplatin 25 mg/m²/day from day 1 to day 3 and 5-FU-continuous infusion for 120 h at a variable dosage from 600 to 1,000 mg/m²/day according to prior radiation. This regimen was repeated every 3 weeks.

Results

A total of 95 patients were enrolled; 92 patients were evaluable for response. The overall response and disease control rates were 78.9 and 93.6 %, respectively. At a median follow-up of 24.8 months, the respective median overall survival (OS) and progression-free survival were 22.7 months (95 % CI 18.6–26.9 months) and 8.6 months (95 % CI 7.7–9.5 months). Toxicities were moderate and manageable. Grade 3/4 toxicities included leucopenia (14.7 %), neutropenia (17.9 %), anemia (3.2 %), thrombocytopenia (6.4 %), nausea (4.2 %), vomiting (9.5 %), stomatitis (9.5 %), diarrhea (3.2 %), aminotransferase (2.2 %) and sensory neuropathy (3.2 %).

Conclusion

Triplet combination chemotherapy with paclitaxel, cisplatin and 5-FU is an effective and safe option in the front-line treatment for recurrent and/or metastatic NPC. The encouraging results with high response rate and long OS suggest that this regimen might be especially considered where tumor shrinkage is required.     

Comparison of second-line treatment outcomes between sensitive and refractory small cell lung cancer patients: a retrospective analysis

Purpose

Small cell lung cancer (SCLC) has a high relapse rate despite being very chemosensitive. The efficacy of second-line treatment is dismal. Our aim was to evaluate the outcome of second-line treatment.

Methods

We retrospectively assessed data of 120 SCLC patients who failed first-line treatment and received second-line treatment at three medical oncology centers.

Results

Median age of group was 58. 82 % had an ECOG PS of 0–1 at the time of relapse. 39 % were at limited stage (LS) at the time of diagnosis. Patients who progressed more than 3 months after first-line therapy were categorized as having platinum-sensitive disease (PSD) (64 %). The number of patients who received platin-based combination treatment was 33 (27 %). The median OS time starting from the initiation of second-line treatment was 7 months. Multivariate analysis identified PS (p = 0.006), extent of disease at diagnosis (0.014) and PSD (0.001) as the independent prognostic factors for survival. Subgroup analyses of the patients with PSD indicated platin rechallenge yields higher progression-free survival, overall survival and overall response rate.

Conclusion

Patients with good ECOG PS,who have PSD or initially presenting with LS, have a good prognosis and in patients with PSD, platinum-based therapy would be more appropriate.     

Multicenter phase II study of S-1 and docetaxel combination chemotherapy for advanced or recurrent gastric cancer patients with peritoneal dissemination

Purpose

Peritoneal dissemination is the most frequent and life-threatening mode of metastasis and recurrence in patients with gastric cancer. A multicenter phase II study was designed to evaluate the efficacy and tolerability of S-1 and docetaxel combination chemotherapy regimen for the treatment of advanced or recurrent gastric cancer patients with peritoneal dissemination.

Methods

Nineteen patients with histologically confirmed unresectable or recurrent gastric cancer with peritoneal dissemination were enrolled. Oral S-1 at 80 mg/m²/day was administered twice daily for 2 weeks, followed by 1 drug-free week. Docetaxel infusion at 40 mg/m² was performed on day 1, simultaneous with S-1 administration. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary endpoints were the response rates and safety status.

Results

Patients received a median of 4 cycles of the S-1 and docetaxel regimen (range 1–43). The disease control rate was 73.7 % (14/19). Median overall survival was 459 days (15.3 months), while median time to progression was 212 days (7.1 months). Neutropenia was the most common type of toxicity (n = 7, 36.8 %).

Conclusions

Combination chemotherapy with S-1 and docetaxel is a tolerable and effective treatment for advanced or recurrent gastric cancer patients with peritoneal dissemination.     

Prognostic significance of c-erbB2 overexpression in patients with metastatic gastric cancer

Background

Overexpression of the gene c-erbB2, which encodes a receptor tyrosine kinase, has been associated with prognosis and response to therapy in several solid tumors. This study was designed to test whether c-erb-B2 overexpression can be related to prognosis of patients with metastatic gastric cancer.

Methods

Between 2005 and 2010, 46 cases of metastatic gastric cancer were evaluated immunohistochemically for c-erb-B2 overexpression. Overall survival (OS) and time-to-progression (TTP) served as the main outcome measures.

Results

c-erbB2 was overexpressed in 19 (41.3 %) cases and 8 patients (17.4 %) had a c-erbB2 score of 3+ (a strong complete membrane staining observed in >10 % of the tumor cells). c-erbB2 expression was not associated with the clinicohistological characteristics of the study participants. The mean OS was 11.48 ± 1.03 months, whereas the mean TTP was 8.28 ± 0.8 months. Compared with patients with a score of 2+ or less (n = 38), those with a c-erbB2 score of 3+ (n = 8) had both a significantly lower OS (15.55 ± 1.63 vs. 8.22 ± 0.88 months, respectively, p < 0.05) and TTP (10.72 ± 1.81 vs. 6.11 ± 0.61 months, respectively, p < 0.05). After allowance for potential confounders, Cox regression analysis identified a c-erbB2 score of 3+ as an independent predictor of both OS (hazard ratio = 1.9; 95 % confidence interval = 1.1?3.7, p < 0.05) and TTP (hazard ratio = 1.8; 95 % confidence interval = 1.1?4.1, p < 0.05).

Conclusion

Our results suggest that c-erbB-2 overexpression may have a prognostic significance in patients with metastatic gastric cancer.     

Carboplatin with weekly docetaxel and ifosfamide in advanced head and neck cancers: a phase I Brown University Oncology Group dose escalation study (HN-93)

Purpose

A phase I study was performed to determine the maximally tolerated dose of carboplatin, ifosfamide, and docetaxel in advanced head and neck cancers.

Methods

Carboplatin (week 1) was administered with weekly docetaxel and ifosfamide for 3 weeks in an every 4-week cycle. Restaging was done after two cycles, while dose level escalation was done in cohorts of three patients.

Results

Fifteen patients (recurrent/metastatic disease, n = 8; bulky locally advanced disease, n = 7) were enrolled. No dose-limiting toxicities were observed. Toxicities included grade 3 neutropenia and anemia (n = 2, each), and grade 2 thrombocytopenia (n = 3). The final level of carboplatin AUC = 6 (week 1) with docetaxel 30 mg/m² per week and ifosfamide 1,000 mg/m² per week was chosen for further evaluation.

Conclusions

This novel regimen of carboplatin with weekly docetaxel and ifosfamide has a favorable toxicity profile and is active in this setting. Phase II study results are awaited.     

Clinical impact of systematic pelvic and para-aortic lymphadenectomy for pT1 and pT2 ovarian cancer: a retrospective survey by the Sankai Gynecology Study Group

Background

The therapeutic value of systematic lymphadenectomy for early-stage epithelial ovarian cancer (EOC) is controversial. This study evaluates the survival impact and adverse events of systematic pelvic and para-aortic lymphadenectomy in patients with pT1 and pT2 EOC.

Methods

A retrospective investigation was performed using data from patients with pT1 and pT2 EOC at multi-institutions belonging to the Sankai Gynecologic Study Group (SGSG). We selected patients who had undergone systematic pelvic and para-aortic lymphadenectomy (Group LA) (n = 284) and patients who had not undergone lymph node resection (Group no-LA) (n = 138). Outcomes for patients and peri-operative adverse events were compared between the two groups.

Results

The median operation time was significantly longer in Group LA (288 min) than in Group no-LA (128 min) (P < 0.0001). Total blood loss was significantly higher in Group LA, 43.7 % of patients receiving blood transfusions. There were no significant differences between the treatment groups for progression-free survival (PFS) or overall survival (OS). However, for patients with pT2, PFS was significantly longer in Group LA than in Group no-LA (P = 0.0150). Lymph node metastases were detected in 23 cases (8.1 %) and these patients had significantly shorter PFS than those without metastasis (P = 0.0409). The outcome for patients who underwent chemotherapy after surgery was significantly improved in the Group no-LA, but no improvement was observed in Group LA.

Conclusions

Systematic lymphadenectomy may improve outcomes only in pT2 EOC patients with acceptable peri-operative events. Furthermore, accurate surgical staging may avoid unnecessary adjuvant chemotherapy in selected early-stage cases.     

Safety and activity of masitinib in combination with gemcitabine in patients with advanced pancreatic cancer

Purpose

To evaluate the efficacy and safety of masitinib combined with gemcitabine in patients with advanced pancreatic cancer.

Patients and methods

Twenty-two non-randomised patients with unresectable, locally advanced (n = 9) or metastatic pancreatic cancer (n = 13) received oral masitinib (9 mg/kg/day) combined with standard gemcitabine. All patients were na?ve to systemic chemotherapy or radiotherapy. The primary endpoint was time-to-progression (TTP) with efficacy and safety analyses performed on the intent-to-treat population. Secondary endpoints included overall survival (OS), as well as, subgroup analyses according to baseline disease, and performance status.

Results

Overall median TTP was 6.4 months (95% CI [2.7–11.7]); 8.3 and 2.7 months, respectively, for locally advanced and metastatic patients; 6.4 and 0.8 months, respectively, for patients with KPS [80–100] or KPS [70]. Median OS was 7.1 months (95% CI [4.8–17.0]); 8.4 and 6.8 months for locally advanced or metastatic patients, respectively; 8.0 and 4.4 months in patients with KPS [80–100] or KPS [70], respectively. The 18-month observed survival rate was similar for locally advanced (22%) and metastatic patients (23%) and reached 28% for KPS [80–100] patients. The most common suspected adverse events were nausea, vomiting, rash, diarrhoea, peripheral oedema, anaemia, lymphopenia, thrombocytopenia, pyrexia, neutropenia, asthenia, leucopoenia, and abdominal pain, and most were of grades 1–2 severity.

Conclusions

The efficacy and safety of masitinib combined with gemcitabine are encouraging, with extended survival and median TTP that support initiation of a phase 3 trial.     

A phase II trial of erlotinib as maintenance treatment after concurrent chemoradiotherapy in stage III non-small-cell lung cancer (NSCLC): a Galician Lung Cancer Group (GGCP) study

Purpose

This single arm, phase II study aims to evaluate the role of epidermal growth factor receptor–tyrosine-kinase inhibitor erlotinib as maintenance therapy following concurrent chemoradiotherapy (cCRT) in unresectable locally advanced non-small-cell lung cancer (NSCLC).

Methods

Patients with unresectable stage IIIA o dry IIIB NSCLC with no evidence of tumor progression after receiving a standard cCRT regimen with curative intent were included. Oral erlotinib 150 mg/day was administered within 4–6 weeks after the end of the cCRT for a maximum of 6 months if no disease progression or intolerable toxicity occurred. Primary end point was the progression-free rate (PFR) at 6 months. Secondary end points included time to progression (TTP) and overall survival (OS).

Results

Sixty-six patients were enrolled and received maintenance treatment with erlotinib [average: 4.5 months (95 % CI 4.0–5.0)]. PFR at 6 months was 63.5 % (41/66). With a median follow-up of 22.7 months (95 % CI 13.5–37.1), the median TTP was 9.9 months (95 % CI 6.2–12.1), and the median OS was 24.0 months (95 % CI 17.3–48.6). Most common adverse events (AEs) related to erlotinib were rash (78.8 %; 16.7 % grade 3), diarrhea (28.8 %; 1.5 % grade 3), fatigue (15.2 %; 1.5 % grade 3), anorexia (7.6 %; 1.5 % grade 3) and vomiting (4.6 %; none grade 3). Five patients (7.6 %) were withdrawn due to AEs.

Conclusions

Erlotinib as maintenance therapy is an active treatment after cCRT in unselected patients with stage III NSCLC, reaching a 6-month PFR of 63.5 % and a median OS of 24 months. The safety profile of maintenance erlotinib was as expected and manageable.     

Possible anti-tumor activity of initial treatment with zoledronic acid with hormonal therapy for bone-metastatic prostate cancer in multicenter clinical trial

Background

To ascertain the anti-tumor effect of zoledronic acid (ZOL) treatment on clinical outcomes in patients with bone metastatic prostate cancer, we examined the effect of ZOL started simultaneously with hormonal therapy as initial treatment in these patients.

Methods

Forty-seven patients with bone-metastatic prostate cancer who received a luteinizing hormone releasing-hormone (LHRH) analogue and an anti-androgen [maximal androgen blockade (MAB)] were assigned to receive ZOL (4 mg intravenous administration every month for 2 years). The time to progression (TTP) of the prostate-specific antigen (PSA), the overall survival (OS), and the rate of PSA decrease in patients with MAB and ZOL treatment (ZOL group) were compared with these parameters in patients who received only MAB at one institute as a control group (non-ZOL group).

Results

Although the nadir PSA level and the rate of PSA normalization showed no significant differences between the ZOL and non-ZOL groups, the time to nadir PSA in the ZOL group was significantly shorter than that in the non-ZOL group (P < 0.05, Mann–Whitney U-test). There was a significant difference in TTP (P = 0.017, log-rank test) between the ZOL and non-ZOL groups, and statistically significant differences in TTP and OS between the ZOL and non-ZOL groups (P = 0.044 and 0.035, log-rank test) were recognized particularly in patients with advanced disease (extension of disease, grade 3 and 4).

Conclusions

Simultaneous administration of ZOL and MAB as initial treatment delayed TTP in bone-metastatic prostate cancer patients. Initial treatment with ZOL has the possibility of anti-tumor activity to delay disease progression.     

Clinical potential of the anticancer drug sensitivity test for patients with synchronous stage IV colorectal cancer

Purpose

We retrospectively evaluated the clinical efficacy and feasibility of a collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to guide therapy for patients with stage IV colorectal cancer (CRC).

Methods

We investigated 38 patients with stage IV CRC. All patients were younger than 85 years and had untreated evaluable metastatic lesions. The primary tumors were surgically resected, and the tissue samples were investigated by CD-DST. Patients treated with in vitro sensitive drugs were defined as Group A (n = 14), while those treated with in vitro non-sensitive drugs were defined as Group B (n = 24). We evaluated response rate (RR), progression-free survival (PFS), and overall survival (OS).

Results

RR was 85.71 % in Group A and 41.67 % in Group B (p = 0.0079). The median PFS was 696.5 days in Group A and 297.5 days in Group B (p = 0.0326). The median OS was 1,023.4 days in Group A and 518.5 days in Group B (p = 0.0061).

Conclusions

The CD-DST can define chemoresistant and chemosensitive tumors. The use of CD-DST might be one of the tools to supplement informed consent prior to initiation of therapy.     

A phase-I trial of pemetrexed plus carboplatin in recurrent ovarian cancer

Background

Carboplatin-based combinations are established in platinum-sensitive recurrent ovarian cancer. To improve the therapeutic index, new platinum-based combinations are required. Pemetrexed is a multi-targeted antifolate inhibiting thymidylate synthase. The aim of this study was to determine the maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) and to characterize toxicities of the combination of pemetrexed (Pem) and carboplatin (Cb).

Design

A standard three-patient cohort dose escalation was performed starting at Cb AUC-5 and Pem 500 mg/m². Patients with platinum-sensitive recurrent ovarian cancer were eligible. Two levels of Cb (AUC-5, 6) and five levels of Pem (500, 600, 700, 800, and 900 mg/m²) were evaluated. DLTs were based on cycle 1.

Results

Twenty patients were enrolled. The median age was 57.4 years (37.3–75.3) and the median platinum-free interval was 26.2 months (7.2–124.4). There was one DLT at dose level 3 in cycle one. No serious adverse events related to the study therapy were observed. The 20 patients completed 112 cycles of Cb (104 were planned) and 115 cycles of Pem (112 were planned). The maximum dose level of Cb AUC-6 and Pem 900 mg/m² was well tolerated. Response rates in 19 patients were: CR: 63.2%; PR: 21.1%; SD; 5.3%, PD: 10.5%.

Conclusions

The combination carboplatin and pemetrexed is safe and well tolerated. A multicenter phase-II trial is currently underway.     

The safety and efficacy of cisplatin plus gemcitabine in recurrent ovarian cancer

Background

The activity and synergy for the combination treatment of cisplatin and gemcitabine has been identified in a variety of human tumor cells, including ovarian cancer cells, and has been widely approved for the treatment of non-small cell lung cancer, pancreatic cancer and biliary tract cancer. As the gastrointestinal symptoms with cisplatin therapy are commonly considered to negatively affect the quality of life of patients more than those experienced with carboplatin therapy, carboplatin is generally preferred over cisplatin in combination therapy. This study evaluated the safety and efficacy of cisplatin plus gemcitabine in patients with recurrent ovarian cancer.

Methods

Patients with recurrent ovarian, peritoneal or fallopian tube cancer, who had failed with multiple other chemotherapy agents, including platinum, received cisplatin (30 mg/m²) plus gemcitabine (750 mg/m²) on days 1 and 8 of every 28 days for between 1 and 4 cycles.

Results

In total, 18 patients were treated with cisplatin and gemcitabine between 2006 and 2011. There were 1 complete and 5 partial responses, producing an overall response rate of 33.4 %. Median overall survival was 11.0 months. Grade 4 neutropenia and thrombocytopenia were seen in 11.1 and 22.2 % of patients, respectively. Non-hematological toxicity was less than Grade 1.

Conclusions

Non-hematological toxicity with combined cisplatin and gemcitabine therapy was considered tolerable and did not impede patient quality of life. However, this drug combination should be monitored for hematologic toxicity.     

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.     

Loss of PTEN expression as a predictor of resistance to anti-EGFR monoclonal therapy in metastatic colorectal cancer: evidence from retrospective studies

Purpose

To investigate the predictive value of loss of PTEN expression in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR monoclonal therapy.

Methods

Studies were systematically identified to investigate the relationship between PTEN expression and clinical outcome in mCRC patients treated with anti-EGFR MoAbs. Clinical outcomes included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated using a fixed-effects model or a random-effects model according to the heterogeneity between the studies.

Results

A total of 852 patients were included in the final meta-analysis. The rate of loss of PTEN expression was 28.4 % (242/852). The overall pooled RR for ORR was 0.413 (95 % confidence intervals (CI), 0.177–0.965) when patients with loss of PTEN expression were compared with those with normal PTEN expression. Anti-EGFR monoclonal therapy resulted in improved PFS (HR, 0.466; 95 % CI, 0.292–0.640) and OS (HR, 0.689 [95 % CI, 0.482–0.896]) in patients unselected by KRAS mutation with normal PTEN expression over loss of PTEN expression. A better prognosis, as reflected by PFS (HR, 0.344; 95 % CI, 0.154–0.533) and OS (HR, 0.544; 95 % CI, 0.285–0.803), was observed in wild-type KRAS patients with normal PTEN expression versus loss of expression.

Conclusions

Loss of expression of PTEN is a potential biomarker for resistance to anti-EGFR monoclonal therapy, particularly in mCRC patients with KRAS wild type.     

Treatment results and prognostic factors for advanced squamous cell carcinoma of the hypopharynx treated with concurrent chemoradiotherapy

Purpose

The purpose of the study is to review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma (SCC) of the hypopharynx and to evaluate the factors affecting survival and larynx preservation.

Study design

Retrospective study.

Methods and materials

The records of 102 patients with Stage III or IV resectable SCC of the hypopharynx treated with CCRT between January 1998 and August 2010 were reviewed. Of the 102 patients, 62 were treated with high-dose regimens including cisplatin, 5-fluorouracil, methotrexate, leucovorin or docetaxel, cisplatin, and 5-fluorouracil. The remaining 40 were treated with low-dose regimens including carboplatin and uracil-tegafur, weekly docetaxel, or S-1. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8–2.0 Gray (Gy), to a total dose of 64.8–70.2 Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan–Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for OS, DSS, and DSS with larynx preservation.

Results

The 5-year OS and DSS for all patients treated with CCRT were 51.3 and 64.3 %, respectively. The 5-year DSS with larynx preservation was 55.5 %. On multivariate analysis, the content of chemotherapy was a significant predictor of OS and DSS for patients undergoing CCRT; N stage was a significant prognostic factor for DSS and larynx preservation.

Conclusion

The treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the N stages of SCC of the hypopharynx.     

A phase II trial of modified weekly irinotecan and cisplatin for chemotherapy-naïve patients with metastatic or recurrent squamous cell carcinoma of the esophagus

Purpose

This phase II study assessed the efficacy and toxicity profile of a modified weekly irinotecan and cisplatin for chemotherapy-naïve patients with metastatic/recurrent esophageal squamous cell carcinoma (SQCC).

Methods

The eligibility criteria included histologically confirmed esophageal SQCC, no prior chemotherapy, adequate organ functions and written informed consent. Patients received irinotecan 65 mg/m² plus cisplatin 30 mg/m² on days 1 and 8, every 3 weeks.

Results

Thirty-two patients were assessed for response and toxicity. Ten patients achieved a partial response (31.3%; 95% CI, 16.0–50.0%). With a median follow-up of 19.0 months, median progression-free and overall survival was 4.4 and 9.6 months, respectively, with a 1-year survival rate of 27.4%. Grade (G) 3/4 neutropenia was observed in 50.0% of the patients, which was the most common cause of dose reduction or therapy delay. G3 non-hematologic toxicity included seven (21.9%) asthenias, four (12.5%) diarrheas, and one (3.1%) nausea/vomiting, but no G4 non-hematologic toxicity was observed.

Conclusions

This modified weekly irinotecan and cisplatin failed to ameliorate hematologic toxicity and to improve efficacy. However, easy administration and favorable non-hematologic toxicity as well as modest anti-tumor activity against metastatic or recurrent esophageal SQCC can make this regimen a potential treatment option, given the complexity of administration and toxicity of conventional infusional 5-FU and cisplatin.