Conversion therapy for inoperable advanced gastric cancer patients by docetaxel,cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study

Background

Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes.

Methods

One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m² b.i.d.) on days 1–14 and intravenous cisplatin (60 mg/m²) and docetaxel (50–60 mg/m²) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery.

Results

Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0–88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS.

Conclusions

DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.

     

A prospective phase II trial of response adapted whole brain radiotherapy after high dose methotrexate based chemotherapy in patients with newly diagnosed primary central nervous system lymphoma-analysis of acute toxicity profile and early clinical outcome

Background

The treatment of primary CNS lymphoma (PCNSL) comprises high dose methotrexate (HDMTX) based chemotherapy followed by whole brain radiotherapy (WBRT), the major drawback of which is long term neurotoxicity. We intended to assess the feasibility of response adapted WBRT in PCNSL in the Indian setting.

Methods

We screened 32 patients and enrolled 22 eligible patients with PCNSL from 2015 to 2017 in a prospective phase II trial. The patients underwent five 2-weekly cycles of induction chemotherapy with rituximab, methotrexate, vincristine, procarbazine. Patients with complete response(CR) to induction chemotherapy were given reduced dose WBRT 23.4 Gy/13 fractions/2.5 weeks while those with partial response (PR), stable or progressive disease (SD or PD) were given standard dose WBRT 45 Gy/25 fractions/5 weeks. Thereafter two cycles of consolidation chemotherapy with cytarabine were given. The primary endpoints of the study were assessment of response rate (RR) and progression free survival (PFS). The secondary endpoints of the study were assessment of overall survival (OS), toxicity profile of treatment and serial changes in quality of life and neuropsychological parameters.

Results

Out of 19 patients who completed HDMTX based chemotherapy, 10 (52.63%) patients achieved CR, 8 (42.11%) patients had PR and 1 patient had PD. After a median follow-up period of 11.25 months, the estimated median OS was 19 months. The actuarial rates of PFS and OS were respectively 94.1 and 68.2% at 1 year and 50.2 and 48.5% at 2 years. Three patients in reduced dose WBRT arm had recurrence and two of them died of progressive disease, whereas there was no recurrence or disease related death in standard dose WBRT arm. On univariate analysis of PFS, age?≤?50 years and use of standard dose WBRT (45 Gy) led to significantly improved outcome (p value 0.03 and 0.02 respectively).

Conclusion

In patients with PCNSL, reduced dose WBRT after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due to higher risk of recurrence, progression and early death. Trial Registration No CTRI/2015/10/006268

     

Do patients with metastatic urothelial carcinoma benefit from docetaxel as second-line chemotherapy?

Purpose

To evaluate the efficacy and toxicity of docetaxel regimen as second-line after failure of a platinum-based chemotherapy.

Methods

Between May 2005 and June 2008, we retrospectively analyzed the data of 22 patients who had evidence of disease progression after one prior platinum-based regimen for metastatic urothelial carcinoma. Patients were treated with two different docetaxel dose schedules: (1) docetaxel 60 mg/m² every 21 days for unfit patients or (2) docetaxel 75 mg/m² every 21 days for fit patients.

Results

Median number of docetaxel cycles was three. Overall disease control rate was 18 %. Of the 22 patients, no patient achieved complete or partial response and four patients had stable disease. Median progression-free survival was 1.67 months and median overall survival was 3.12 months. Neutropenia was the most common adverse event.

Conclusions

This study identifies that docetaxel as second-line chemotherapy has low activity and was associated with significant toxicity.

     

Comparative efficacy and toxicity of induction chemotherapy with concurrent stereotactic body radiotherapy and stereotactic body radiotherapy with subsequent chemotherapy in patients with clinical stage T1-3N0M0 non-small cell lung carcinoma

Purpose

We compared the clinical efficacy and toxicity of stereotactic body radiotherapy with induction chemotherapy and concurrent radiochemotherapy vs stereotactic body radiotherapy with subsequent chemotherapy in patients with clinical stage T1-3N0M0 non-small cell lung carcinoma.

Methods

We retrospectively analyzed 38 patients with c-stage T1-3N0M0 non-small cell lung carcinoma who received stereotactic body radiotherapy. All patients received six cycles of chemotherapy. Fifteen of the patients were treated with three cycles of induction chemotherapy, one cycle of concurrent radiochemotherapy, and then two cycles of consolidation chemotherapy, while 23 patients received Sequential Radiotherapy/Chemotherapy.

Results

Patients in the induction chemotherapy group experienced a longer duration of esophagitis (median 2 vs 0, range 0–6 vs 0–3.6 weeks, p = 0.04). We divided the patients into two groups based on their median pre-treatment tumor volume (cm³): >32.11 and ≤32.11. The tumor response rate in patients with larger tumor volume was substantially higher in the induction chemotherapy group than in the Sequential Radiotherapy/Chemotherapy group (66.67 vs 40%). Among patients with pre-treatment tumor volume (cm³) >32.11, the median local progression-free survival (LPFS) in the induction chemotherapy group and Sequential Radiotherapy/Chemotherapy group was 18 months (range 7–72 months) and 11 months (range 6–53 months), respectively. There was a statistically significant difference between the two groups (p = 0.006).

Conclusions

Simultaneous SBRT and chemotherapy can result in a longer duration of esophagitis. However, for patients with large tumor volume, ICT combined with concurrent radiochemotherapy may result in better local tumor response as well as longer LPFS and progression-free survival. To better elucidate the best treatment, further clinical trials are needed.

     

Evaluation the Survival of Patients with Gastric Cancer Treated with Adjuvant or Palliative Chemotherapy

Aim

Our aim was to evaluate impact of chemotherapy (5-fluorouracil plus docetaxel and cisplatin) on the survival of gastric cancer cases.

Method

Seventy-nine patients were eligible to take part in this study between November 2006 and April 2013, who received 5-fluorouracil (700 mg/m², 21-h infusion within 5 days), cisplatin (60 mg/m² on day 3), and Docetaxel (60 mg/m² on day 2). Radiotherapy was added to the treatment only in the cases with entire stomach body cancer (positive margin) and with giant ulcer (above 50 mm) in proximal gastric cancer.

Results

Twenty-four patients were female and 55 were male. The median age was 54. In this study, 54 % of the tumors were located in the proximal and 46 % in the distal of stomach. Seventy five percent of patients were at stage I–III (adjuvant chemotherapy), and 25 % at stage IV (palliative chemotherapy). Ninety-one percent of the patients at stages I–II, 68.3 % of the patients at stage III, and one out of 20 patients at stage IV were alive at the end of follow-up. Median disease-free survival for the patients at stages I–III was 63 months, and the overall survival for all patients was 50 months.

Conclusion

The results of our study indicate that the survival of the patients with stomach cancer increases with chemotherapy. Radiotherapy was used for our patients with gastric cancer in specific cases.

     

Concurrent chemoradiation for locally advanced stage III non-small cell lung cancer with cisplatin,vinorelbine, and thoracic radiotherapy: a phase II study from the Galician Lung Cancer Group

Purpose

The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS).

Materials and methods

A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m² and intravenous vinorelbine 25 mg/m² on day 1 and oral vinorelbine on day 8 (60 mg/m²)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week).

Results

ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported.

Conclusion

This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.

     

A phase II study of combination therapy with oral S-1 and cisplatin in elderly patients with advanced gastric cancer

Background

A combination of S-1 and cisplatin is recognized as one of the standard first-line chemotherapy regimens for patients with advanced gastric cancer. However, demographic analyses of pivotal phase III studies have showed that only a minority of treated patients were aged 76 years or older. The purpose of this phase II study was to evaluate the safety and efficacy of combination therapy with S-1 and cisplatin in elderly patients with chemotherapy-naive advanced gastric cancer.

Methods

Patients aged 76 years or older received S-1 40 mg/m² orally twice daily for 21 days and cisplatin 60 mg/m² intravenously infused at day 8 of each 35-day cycle. Dose modification was performed according to creatinine clearance. The primary endpoint was overall survival (OS). Secondary endpoints included response rate, progression-free survival (PFS), time to treatment failure (TTF), and adverse events.

Results

A total of 40 patients were enrolled. Median OS was 12.3 months, PFS was 7.8 months, and TTF was 4.3 months. The response rate was 54%. The most common grade 3–4 adverse events were anorexia (25%), neutropenia (23%), hyponatremia (20%), anemia (18%), and febrile neutropenia (8%). No treatment-related death occurred.

Conclusions

Combination chemotherapy with S-1 and cisplatin is an effective and well-tolerated regimen for elderly patients with advanced gastric cancer when the dose is adjusted according to renal function.

     

A phase II trial of capecitabine plus cisplatin (XP) for patients with advanced gastric cancer with early relapse after S-1 adjuvant therapy: XParTS-I trial

Backgrounds

In Japan, standard regimens for advanced gastric cancer (AGC) include S-1 chemotherapy. The standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine alone is platinum-based chemotherapy, while the standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine plus platinum is second-line chemotherapy. To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment for AGC patients who relapse within 6 months after S-1-based therapy, we conducted a multicenter phase II trial (NCT01412294).

Methods

HER2-negative gastric cancer patients treated with adjuvant chemotherapy including S-1 for more than 12 weeks and relapsed within 6 months were treated with capecitabine 1000 mg/m² bid for 14 days plus cisplatin 80 mg/m² on day 1 of a 3-week cycle. The primary endpoint was PFS; secondary endpoints were OS, time to treatment failure, overall response rate (ORR) and safety.

Results

Forty patients (median age 64) were enrolled; of those, 37 (92.5%) received adjuvant S-1 monotherapy. Median PFS was 4.4 months (95% CI 3.6–5.1), which was longer than the 2-month protocol-specified threshold (p < 0.001). Median OS was 13.7 months (95% CI 9.0–17.7) and ORR was 8/30 (26.7%) (95% CI 14.2–44.4). Most common grade ≥ 3 adverse events were neutropenia (23%), anemia (18%), elevated serum creatinine (18%), fatigue (13%), diarrhea (7.5%), and anorexia (7.5%).

Conclusions

XP was safe and effective in patients with early relapse after S-1 adjuvant chemotherapy for curatively resected gastric cancers. XP may be a good option for the treatment of patients after early failure after adjuvant S-1.

Trial registration

NCT01412294.

     

Pemetrexed for primary central nervous system lymphoma in the elderly

Objective

The aim of this study was to evaluate the efficacy and safety of a consecutive series of elderly patients with primary central nervous system lymphoma (PCNSL) treated with single-agent pemetrexed without radiotherapy or intrathecal chemotherapy.

Methods

Twelve histologically confirmed newly diagnosed PCNSL patients older than 65 years were studied between 2008 and 2013. An induction chemotherapy was initially given (pemetrexed 600 mg/m² on day 1, every 3 weeks). Patients achieving a complete, partial response or stable disease proceeded to a maintenance phase (up to 6 cycles). Patients with progressive/recurrent disease (PD) were treated with whole brain radiotherapy on an individual basis.

Results

Four patients presented complete response, six patients showed partial response and two patients presented progressive disease. The median progression-free survival (PFS) was 9.0 months [95 % confidence interval (CI) 2.0–45.3] and the median overall survival was 19.5 months (95 % CI 5.0–45.3). Adverse events included leukocytopenia, anemia, fatigue, rash and vomiting. No neurotoxicity or treatment-related death was observed. The estimated 1-year and 2-year survival rate was 66.7 and 41.7 %, respectively.

Conclusions

Our efficacy results demonstrate that the single-agent pemetrexed was feasible, active and well tolerated in elderly patients with PCNSL. Furthermore, this single-agent regimen results in higher response rates and less toxicity comparable with other chemotherapy or radiotherapy regimens. Prospectively, controlled studies are warranted to confirm such results.

     

Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, <Emphasis Type="Italic">nab</Emphasis>-Paclitaxel,Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis

Background

Continuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic.

Objective

In this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy.

Patients and Methods

Since July of 2008, we have treated 65 patients with 5FU (180 mg/m²/day × 14 days) via an ambulatory pump. Calcium leucovorin (20 mg/m² IV), nab-paclitaxel (60 mg/m²) IV as a 30-min infusion, and oxaliplatin (50 mg/m²) IV as a 60-min infusion were given on days 1, 8, and 15. Bevacizumab (5 mg/kg) IV over 30 min was administered on days 1 and 15. Cycles were repeated every 28–35 days. There were 42 women and 23 men, and the median age was 59 years. Forty-six patients had stage IV disease.

Results

The median survival was 19 months, with 82% of patients surviving 12 months or longer. The overall response rate was 49%. There were 28 patients who had received prior treatment, 15 of whom responded to therapy. Fifty-two patients had elevated CA 19-9 prior to treatment. Of these, 21 patients had 90% or greater reduction in CA 19-9 levels. This cohort had an objective response rate of 71% and a median survival of 27 months. Thirty patients stopped treatment due to disease progression, and an additional 22 stopped because of toxicity. One patient died while on therapy.

Conclusions

This non-gemcitabine-based regimen resulted in higher response rates and better survival than what is commonly observed with therapy given at conventional dosing schedules. Low-dose continuous (metronomic therapy) cytotoxic chemotherapy combined with antiangiogenic therapy is safe and effective.

     

Bi-weekly eribulin therapy for metastatic breast cancer: a multicenter phase II prospective study (JUST-STUDY)

Background

This study aimed to investigate whether schedule modification is safe and effective in patients intolerant to the standard eribulin dose and schedule.

Methods

Patients with metastatic breast cancer (MBC) treated with both anthracycline and taxane and ≤ 3 prior regimens of chemotherapy for MBC received eribulin at the standard dose and schedule (1.4 mg/m² on days 1 and 8 of a 21-day cycle) in the first cycle; change of dosing schedule (1.4 mg/m² on days 1 and 15 of a 28-day cycle) was determined by change in neutrophil count, platelet count, aspartate aminotransferase, alanine aminotransferase, total bilirubin, serum creatinine, and non-hematological toxicity on day 8 of the first cycle or day 1 of the second cycle. Clinical benefit rate (CBR; primary endpoint), time to treatment failure (TTF), overall survival (OS), and safety were evaluated.

Results

Of the 88 patients who were enrolled and received standard eribulin therapy in the first cycle, 42 patients were moved to the bi-weekly therapy group and 40 continued standard therapy. In the bi-weekly and standard therapy groups, mean relative dose intensity was 62.7 and 90.9%, CBR was 31.0 and 25.0%, median TTF was 81.5 and 75 days, and OS was 523 and 412 days, respectively. Neither group reported severe adverse events.

Conclusion

This is the first study to show that a bi-weekly eribulin schedule is tolerable and has comparable efficacy in patients intolerant to the standard eribulin schedule.

Clinical trial registration

University Hospital Medical Information Network (UMIN) Center (ID: UMIN 000008491).

     

Neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for stage IB2, IIA2, and IIB patients with non-squamous cell carcinoma of the uterine cervix

Background

We conducted a phase II study to evaluate the efficacy of neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for patients with non-squamous cell carcinoma of the uterine cervix.

Methods

Sixty-one patients with International Federation of Gynecology and Obstetrics stage IB2, IIA2, or IIB non-squamous cell carcinoma of the uterine cervix were enrolled. The patients were administered docetaxel at a dose of 60 mg/m², followed by carboplatin at a dose based on an area under the curve of 6. The treatments were repeated every 21 days for one to three cycles. Fifty-two patients were eligible to evaluate the efficacy of neoadjuvant chemotherapy followed by radical hysterectomy. Adverse events were evaluated in 59 patients.

Results

The response rate was 69 % (95 % CI, 57–82 %), with 5 patients achieving complete response, 31 partial response, 15 stable disease, and 1 progressive disease. Median follow-up duration was 1913 days with a range of 145–2632 days. Of 52 patients, 50 underwent radical hysterectomy after neoadjuvant chemotherapy. The 2-year overall survival rate was 81.8 % for stage IB2, 85.7 % for stage IIA2, and 92.6 % for stage IIB. The most frequent grade 3 and 4 hematological toxicity was neutropenia, with 43 patients experiencing grade 4 and 11 with grade 3. The nonhematological toxicities were mainly grade 1 or 2 in severity.

Conclusion

Neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy may be a useful strategy for patients with non-squamous cell carcinoma of uterine cervix.

     

Multicenter randomized phase II clinical trial of oxaliplatin reintroduction as a third- or later-line therapy for metastatic colorectal cancer—biweekly versus standard triweekly XELOX (The ORION Study)

Background

The aim of this multicenter, open-label, randomized phase II trial was to evaluate the efficacy of a dose-dense capecitabine and oxaliplatin (XELOX) regimen in patients with metastatic colorectal cancer (mCRC) for whom reintroduction of oxaliplatin had been planned as a third- or later-line regimen.

Methods

The patients with mCRC who had received prior chemotherapy including oxaliplatin and were scheduled for reintroduction of oxaliplatin were randomized to capecitabine (1,000 mg/m²) twice daily on days 1–14 and oxaliplatin (130 mg/m²) on day 1 every 21 days (Q3W group) or capecitabine (2,000 mg/m²) twice daily on days 1–7 and oxaliplatin (85 mg/m²) on day 1 every 14 days (Q2W group). The primary endpoint was the time-to-treatment failure (TTF). Other endpoints included overall survival (OS), progression-free survival (PFS) and other adverse events (AEs).

Results

A total of 46 patients were enrolled in the trial—22 patients were randomly assigned to the Q3W group and 23 to the Q2W group. The median TTF was 3.4 months in both groups (hazard ratio [HR] 1.053; p = 0.880). The median PFS and OS were 3.3 and 9.2 months in the Q2W group and 4.3 and 12.1 months in the Q3W group, respectively (HR 1.15; p = 0.153 and 0.672; p = 0.836). The most common grade 3?4 AEs in the Q3W and Q2W groups were fatigue (27.3 vs 21.7), neuropathy (9.1 vs 0 %) and diarrhea (9.1 vs 0 %), respectively.

Conclusion

There was no significant inter-group difference in any of the efficacy and safety endpoints, including TTF, OS, RFS and AEs. The results of this clinical trial were convincingly negative.

     

A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in the recent treatment strategy for patients with metastatic or recurrent esophageal squamous cell carcinoma

Background

Patients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, the most widely used first-line chemotherapy regimen for these patients has been the combination of 5-fluorouracil + cisplatin (CF). However, prognostic factors of CF as first-line chemotherapy for ESCC have not been clarified.

Methods

A total of 187 patients with metastatic or recurrent esophageal ESCC treated with CF at the National Cancer Center Hospital between January 2001 and December 2012 were enrolled in the study. The CF regimen comprised cisplatin (80 mg/m²) administered on day 1 and 5-fluorouracil (800 mg/m²) administered continuously on days 1–5, every 4 weeks. Multivariate Cox regression analysis was used to determine the potential prognostic factors.

Results

The median age of the patients was 62 (range 34–84) years. Metastasis and recurrence occurred in 116 and 71 of these patients, respectively. The overall response rate was 37.2%, with median progression-free and overall survival times of 4.8 and 10.4 months, respectively. In the multivariate analysis, higher serum C-reactive protein level and lower serum albumin level at the time of CF treatment initiation and number of metastatic sites were identified as independent prognostic factors for survival.

Conclusions

The results of this study corroborate previous findings on the efficacy of CF and will aid physicians in clinical decision-making and individual patient risk stratification, as well as in the further development of chemotherapy regimens.

     

Feasibility of adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 for completely resected non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 1001

Background

This multicenter study evaluated the feasibility of novel adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent, long-term maintenance with S-1 in patients with completely resected stage II–IIIA non-small-cell lung cancer (NSCLC).

Methods

Patients received four cycles of S-1 (80 mg/m²/day for 2 weeks, followed by 2 weeks rest) plus carboplatin (area under the curve 5, day 1) followed by S-1 (80 mg/m²/day for 2 weeks, followed by a 1-week rest). Patients unable to continue S-1 plus carboplatin because of severe toxicity converted to single-agent S-1 maintenance. The duration of adjuvant chemotherapy was 10 months in both situations. The primary endpoint was feasibility, defined as the proportion of patients who completed four cycles of S-1 plus carboplatin and single-agent S-1 maintenance for 10 months. The treatment completion rate was determined; treatment was considered feasible if the lower 90% confidence interval (CI) was ≥50%.

Results

Eighty-nine patients were enrolled, of whom 87 were eligible and assessable. Seventy-eight patients (89.7%) completed four cycles of S-1 plus carboplatin and 55 (63.2%) completed the following S-1 maintenance therapy for a total of 10 months. The treatment completion rate was 63.2% (90% CI, 54.4–71.2%), indicating feasibility. There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (13.8%), thrombocytopenia (11.5%), and anorexia (4.6%). The 2-year relapse-free survival rate was 59.8%.

Conclusions

We concluded that adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 is feasible and tolerable in patients with completely resected NSCLC.

Clinical registration number

UMIN000005041.

     

Efficacy of intrathecal chemotherapy in patients with central nervous system involvement of hematological malignancies: a retrospective analysis

Introduction

Central nervous system (CNS) involvement, especially involvement of the cerebrospinal fluid (CSF), is common in several haematological malignancies. Intrathecal (IT) chemotherapy can be used to manage CSF involvement.

Methods

Here we evaluated the effectiveness of IT chemotherapy among 80 patients with haematological malignancies and CSF localization who were treated with IT chemotherapy from 2001 to 2012.

Results

The majority of patients was diagnosed with diffuse large B-cell lymphoma (26%) or acute lymphoblastic leukaemia/lymphoblastic lymphoma (19%). After first-line IT chemotherapy, which mainly consisted of methotrexate (MTX) and corticosteroids, CSF complete response (CSF CR) was achieved in 76% of patients. 91% reached CSF CR when including second-line IT-chemotherapy. Clinical response was documented in 75%. Although most patients were additionally treated with systemic chemotherapy, response rate did not differ between patients treated with CNS-penetrating and CNS-non-penetrating drugs. CNS progression/relapse occurred in 40% of patients with median progression-free survival of 12.2 months. The median overall survival was 18.3 months; 55% of the patients died during follow-up.

Conclusions

Our analysis shows a high response rate after first-line IT chemotherapy, but also a relatively high progression/relapse percentage.

     

A phase II study of preoperative chemotherapy with docetaxel,cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002

Background

Gastric cancer with extensive lymph node metastasis is commonly considered unresectable, with a poor prognosis. We previously reported the results of the use of cisplatin and S-1 as preoperative chemotherapy for gastric cancer with extensive lymph node metastasis; docetaxel, cisplatin, and S-1 (DCS) have now been investigated for the same purpose.

Methods

Patients received two or three 28-day cycles of DCS therapy (docetaxel at 40 mg/m² and cisplatin at 60 mg/m² on day 1, S-1 at 40 mg/m² twice daily for 2 weeks) followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was given for 1 year. The primary end point was the response rate (RR) to preoperative chemotherapy determined by central peer review according to the Response Evaluation Criteria in Solid Tumors version 1.0. The planned sample size was 50, with one-sided alpha of 10 %, power of 80 %, expected RR of 80 %, and threshold of 65 %.

Results

Between July 2011 and May 2013, 53 patients were enrolled, of whom 52 were eligible. The clinical RR was 57.7 % [30/52, 80 % confidence interval 47.9–67.1 %, p = 0.89], and R0 resection was achieved in 84.6 % of patients (44/52). Common grade 3 or grade 4 adverse events during DCS therapy were leukocytopenia (18.9 %), neutropenia (39.6 %), and hyponatremia (15.1 %). The common grade 3 or grade 4 surgical morbidity was abdominal infection (10.2 %). The pathological RR was 50.0 % (26/52).

Conclusions

Preoperative DCS therapy was feasible but did not show a sufficient RR. Preoperative cisplatin and S-1 therapy is still considered the tentative standard treatment for this population until survival results are known.

     

Salvage treatment with irinotecan/cisplatin versus pemetrexed/cisplatin in patients with non-small cell lung cancer pre-treated with a non-platinum-based regimen in the first-line setting: a randomized phase II study of the Hellenic Oncology Research Group (HORG)

Background

Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine.

Patients and methods

A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m² on day 1 and 100 mg/m² on day 8 plus cisplatin 80 mg/m² on day 8 every 3 weeks (IC arm) or pemetrexed 500 mg/m² plus cisplatin 80 mg/m² on day 1 every 3 weeks (PC arm). The primary endpoint of the study was the overall response rate (ORR).

Results

The ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3 months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns). Median overall survival (OS) was significantly higher in patients with PC (6.9 vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC, with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs. 31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018).

Conclusions

In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin is associated with increased OS and is better tolerated than the combination of irinotecan/cisplatin and should be considered as a valid therapeutic option for platinum-naive, previously treated patients.

ClinicalTrials.gov Identifier

NCT00614965.

     

Regional differences in advanced gastric cancer: exploratory analyses of the AVAGAST placebo arm

Background

AVAGAST was an international, randomized, placebo-controlled phase III study of chemotherapy with or without bevacizumab as first-line therapy for patients with advanced gastric cancer. We performed exploratory analyses to evaluate regional differences observed in the trial.

Methods

Analyses were performed in the placebo plus chemotherapy arm (intention-to-treat population). Chemotherapy was cisplatin 80 mg/m² for six cycles plus capecitabine (1000 mg/m² orally bid days 1–14) or 5-fluorouracil (800 mg/m²/day continuous IV infusion days 1–5) every 3 weeks until disease progression or unacceptable toxicity.

Results

Overall, 387 patients were assigned to placebo plus chemotherapy (eastern Europe/South America, n = 118; USA/western Europe, n = 81; Korea/other Asia, n = 94; Japan, n = 94). At baseline, poor performance status, liver metastases, and larger tumors were most frequent in eastern Europe/South America and least frequent in Japan. Patients received subsequent chemotherapy after disease progression as follows: eastern Europe/South America (14%); USA/western Europe (37%); Korea/other Asia (61%); and Japan (77%). Hazard ratios for overall survival versus USA/western Europe were 1.47 (95% CI, 1.09–1.99) for eastern Europe/South America, 0.91 (95% CI, 0.67–1.25) for Korea/other Asia, and 0.87 (95% CI, 0.64–1.19) for Japan.

Conclusions

Regional differences in the healthcare environment may have contributed to the differences in overall survival observed in the AVAGAST study.

     

Treatment of childhood astrocytomas with irinotecan and cisplatin

Background

Previously we described the outcome of children with spinal cord astrocytoma treated with irinotecan and cisplatin (I/C). We here report the review of the initial institutional experience using this combination for children with low-grade glioma (LGG).

Procedure

I/C chemotherapy consisted of weekly cisplatin (30 mg/m²) and irinotecan (50–65 mg/m²) for a total maximum of 16 doses, administered in an outpatient basis.

Results

Between November 2002 and December 2009, 46 children (median age 6.3 years; range 0.3–17.7) with glioma were treated. We here report the cohort of 31 patients with LGG. Patients received a median of 16 cycles of I/C (range 8–16). The overall objective response [complete response (CR) + partial response (PR)] and disease control (CR + PR + stable disease) rates to I/C treatment were 6.5% [95% confidence interval (CI), 0.8–21.4%] and 93.5% (95% CI 78.6–99.2%), respectively. Disease control persisted for a median of 65 months. Toxicity was predominantly myelosuppression only seen in heavily pretreated patients. Survival analysis shows 5-year event-free survival (EFS) of 54% and 5-year overall survival (OS) of 80%.

Conclusion

I/C chemotherapy produced disease control and clinical improvement in a majority of children with low-grade glioma, with manageable toxicity.