Effect of Talactoferrin Alfa on the Immune System in Adults With Non‐Small Cell Lung Cancer

Background.

Talactoferrin alfa (talactoferrin), an agent with immune-stimulating properties, has demonstrated safety and preliminary efficacy in clinical trials.

Methods.

Ten patients (five males and five females) with stage IV non-small cell lung cancer (NSCLC) in a single-arm pilot study received orally administered talactoferrin (1.5 g, b.i.d.) for up to 24 weeks. Radiographic and immunologic studies were performed at baseline and at weeks 6 and 12. Circulating immune cells (natural killer cells [NKCs], CD4⁺, CD8⁺, and regulatory T cells) and systemic cytokine levels were measured to assess immune response.

Results.

Patients enrolled in the study had received a median of four prior chemotherapy regimens, and all patients were symptomatic. Talactoferrin was well tolerated, with no grade 3 or 4 toxicities. Median time to progression (TTP) and overall survival were 6 weeks and 14.5 weeks, respectively. The four patients with ≥9 weeks TTP had evidence of immunologic activity (three with increased NKC activity).

Conclusions.

The median of four previous chemotherapy regimens, with elevated levels of interleukin (IL) 6 and tumor necrosis factor-alfa in most patients, suggests these patients were poor candidates for immunotherapy.     

Long‐Term Survival in Patients with Metastatic Melanoma Treated with DTIC or Temozolomide

Background.

Patients with metastatic melanoma typically have a poor outcome; however, a small proportion of patients achieve long-term survival (LTS). It is unclear how often LTS is related to sensitivity to chemotherapy.

Methods.

All patients with metastatic melanoma treated with either dacarbazine (DTIC) or temozolomide (TMZ) at the British Columbia Cancer Agency (BCCA) from January 1, 1988 to February 1, 2006 were identified through the BCCA pharmacy electronic database, which was then linked to the surveillance and outcomes unit to identify patients with LTS, defined as survival ≥18 months following chemotherapy.

Results.

In total, 397 patients were treated with either DTIC (n = 349) or TMZ (n = 48) and 43 patients (10.8%) were identified with LTS. Two additional patients with LTS were added prior to 1988 for a total of 45 patients. The 5-year overall and progression-free survival rates for patients with LTS were 33% and 16%, respectively. In total, 16% had a complete response (CR) to chemotherapy, which was the only factor identified that correlated with survival in the multivariate analysis. However, most patients with LTS had an incomplete response to chemotherapy.

Conclusions.

LTS occurs in select patients who achieve a CR to chemotherapy. However, this occurs in only a minority of patients and, in most cases, the longer survival is likely the result of indolent disease biology or host factors.     

Addition of rituximab is not associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma

Background

The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma (DLBCL) remains to be defined. We aimed to compare CHOP plus rituximab (R-CHOP) with CHOP alone and determine the value of radiotherapy in these patients.

Methods

Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study.

Results

Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response (CR) rate was 77% both in R-CHOP and CHOP groups (P=0.945). After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival (PFS) (76% vs. 85%; log-rank P=0.215) and 5-year overall survival (OS) (90% vs. 96%; log-rank P=0.175) compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone (86% vs. 71%; log-rank P=0.005). At multivariate analysis, patients who had CR (P=0.008) and received radiotherapy (P=0.003) were significantly associated with superior PFS.

Conclusions

CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients.     

Fluorine‐18‐Fluorodeoxyglucose Positron Emission Tomography in Response Assessment Before High‐Dose Chemotherapy for Lymphoma: A Systematic Review and Meta‐Analysis

Background.

We conducted a systematic review and meta-analysis to better define the prognostic ability of fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) following salvage chemotherapy for relapsed or refractory Hodgkin''s lymphoma (HL) and aggressive non-Hodgkin''s lymphoma.

Methods.

We searched PubMed (from inception to January 31, 2010), bibliographies, and review articles without language restriction. Two assessors independently assessed study characteristics, quality, and results. We performed a meta-analysis to determine prognostic accuracy.

Results.

Twelve studies including 630 patients were eligible. The most commonly evaluated histologies were diffuse large B-cell lymphoma (n = 313) and HL (n = 187), which were typically treated with various salvage and high-dose chemotherapy regimens. Studies typically employed nonstandardized protocols and diagnostic criteria. The prognostic accuracy was heterogeneous across the included studies. ¹⁸F-FDG PET had a summary sensitivity of 0.69 (95% confidence interval [CI], 0.56–0.81) and specificity of 0.81 (95% CI, 0.73–0.87). The summary estimates were stable in sensitivity analyses. In four studies that performed direct comparisons between PET and conventional restaging modalities, PET had a superior accuracy for predicting treatment outcomes. Subgroup and metaregression analyses did not identify any particular factor to explain the observed heterogeneity.

Conclusion.

¹⁸F-FDG PET performed after salvage therapy appears to be an appropriate test to predict treatment failure in patients with refractory or relapsed lymphoma who receive high-dose chemotherapy. Some evidence suggests PET is superior to conventional restaging for this purpose. Given the methodological limitations in the primary studies, prospective studies with standardized methodologies are needed to confirm and refine these promising results.     

Dose‐Dense FEC Followed by Dose‐Dense Ixabepilone as Neoadjuvant Treatment for Breast Cancer Patients: A Feasibility Study

Background.

Ixabepilone is an effective chemotherapy in metastatic breast cancer that has been pretreated with anthracyclines and is resistant or refractory to taxanes. Adjuvant dose-dense (DD) chemotherapy is more effective than regimens administered every 3 weeks, especially in hormonal receptor (HR)-negative tumors.

Methods.

A feasibility study of neoadjuvant DD ixabepilone was conducted in breast cancer patients with tumors measuring at least 2 cm. Patients received 5-fluorouracil 600 mg/m², epirubicin 90 mg/m², and cyclophosphamide 600 mg/m² (“FEC” in combination) administered intravenously on day 1 every 14 days with granulocyte-colony stimulating factor (filgrastim) followed by ixabepilone 40 mg/m² administered intravenously on day 1 every 14 days with granulocyte-colony stimulating factor. The study''s primary endpoint was feasibility, and the secondary endpoint was pathologic complete response. A two-stage Simon''s design was adopted.

Results.

Forty-seven patients were enrolled, and 42 were evaluable. For 10 of 42 patients, DD ixabepilone was not feasible. Six (14%) required ixabepilone interruption, and four (9.5%) required ixabepilone dose reduction of 25%. One toxic death occurred. Hematologic grade 3–4 toxicities included anemia (9.5%), grade 4 neutropenia (2.4%), febrile neutropenia (4.8%), and thrombocytopenia (2.4%). Nonhematologic grade 3–4 toxicities consisted of fatigue (14.3%), mucositis (14.3%), sensory neuropathy (7.1%), onychopathy (7.1%), and liver toxicity (4.8%). Grade 2 sensory neuropathy lasting longer than 7 days was recorded in 11.9% of patients. Pathologic complete response was observed in 16 of 42 patients (38.1%), including 11 of 23 (47.8%) with HR-negative tumors and 5 of 19 (26.3%) with HR-positive tumors.

Conclusion.

Despite high activity, DD ixabepilone after DD FEC is poorly tolerated.     

A Randomized Phase II Study of Carboplatin With Weekly or Every‐3‐Week Nanoparticle Albumin‐Bound Paclitaxel (Abraxane) in Patients With Extensive‐Stage Small Cell Lung Cancer

Background.

Platinum plus etoposide is the standard therapy for extensive-stage small cell lung cancer (ES-SCLC) and is associated with significant myelosuppression. We hypothesized that the combination of carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) would be better tolerated. We investigated carboplatin with nab-paclitaxel on every-3-week and weekly schedules.

Methods.

This noncomparative randomized phase II trial used a two-stage design. The primary objective was objective response rate, and secondary objectives were progression-free survival, overall survival, and toxicity. Patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status ≤2 and no prior chemotherapy were randomized in a 1:1 ratio to arm A (carboplatin area under the curve [AUC] of 6 on day 1 and nab-paclitaxel of 300 mg/m² on day 1 every 3 weeks) or arm B (carboplatin AUC of 6 on day 1 and nab-paclitaxel 100 mg/m² on days 1, 8, and 15 every 21 days). Response was assessed after every two cycles.

Results.

Patients required frequent dose reductions, treatment delays, and omission of the weekly therapy. The trial was closed because of slow accrual.

Conclusion.

Carboplatin and nab-paclitaxel demonstrated activity in ES-SCLC but required frequent dose adjustments.     

Efficacy of chemotherapy in metastatic male breast cancer patients: a retrospective study

Background

The role of chemotherapy in the treatment of metastatic male breast cancer patients remains unknown, and the only available evidence stem from small, retrospective series evaluating outdated drugs and/or regimens.

Methods

In this retrospective study we evaluated the activity of polychemotherapy, consisting of three-drug (anthracycline-containing and anthracycline-free) regimens, as a first-line therapy for metastatic male breast cancer patients who had received at least one prior endocrine therapy.

Results

Fifty patients treated between 1978 and 2013 were included in the present analysis. Regarding best response, we recorded 1 (2%) complete response and 27 (54%) partial responses, for an overall response rate of 56% (95% CI, 42.2-69.8). Considering stable disease, the disease control rate was 84%. Median progression-free survival was 7.2 months (95% CI, 5.9-8.5), and median overall survival was 14.2 months (95% CI, 12.2-16.2). Albeit we observed some differences for all the outcomes explored when comparing anthracycline-containing and anthracycline-free regimens, they were not statistically significant.

Conclusions

Chemotherapy, consisting in both anthracycline-containing and anthracycline-free regimens, showed encouraging antitumor activity in metastatic male breast cancer patients previously treated with endocrine therapy.     

A Phase II Study of Capecitabine,Oxaliplatin, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas

Background.

Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.

Methods.

Thirty-seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m² BID on days 1–14, and oxaliplatin 130 mg/m² with bevacizumab 15 mg/kg on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin-1 (NRP1) and -2 (NRP2) mRNA expression was evaluated in archived tumor.

Results.

Thirty-five patients were evaluable for efficacy. Median PFS was 7.2 months; median OS was 10.8 months. RR was estimated at 51.4%. The regimen was tolerable with expected drug class-related toxicities. NRP2 mRNA levels significantly correlated with PFS (p = 0.042) and showed a trend toward significance with OS (p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome.

Conclusions.

Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumab-containing regimens in metastatic gastroesophageal cancer.     

Myeloablative Anti-CD20 Radioimmunotherapy +/- High-Dose Chemotherapy Followed by Autologous Stem Cell Support for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival

Background

Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell infusion (ASCT) enables high radiation doses to lymphoma sites. We performed a phase I/II trial to assess feasibility and survival.

Methods

Twenty-three patients with relapsed/refractory NHL without complete remission (CR) to salvage chemotherapy were enrolled to evaluate RIT with Iodine-131 labelled rituximab (¹³¹I-rituximab) in a myeloablative setting. Biodistribution and dosimetric studies were performed to determine ¹³¹I activity required to induce a total body dose of 21-27Gy to critical organs. In 6/23 patients RIT was combined with high-dose chemotherapy. 8/23 patients received a sequential high-dose chemotherapy with a second ASCT. The median follow-up is 9.5 years.

Results

6.956-19.425GBq of ¹³¹I was delivered to achieve the limiting organ dose to lungs or kidneys. No grade III/IV non-hematologic toxicity was seen with RIT alone. Significant grade III/IV toxicity (mucositis, fever, infection, one therapy related death) was observed in patients treated with RIT combined with high-dose chemotherapy. The overall response rate was 87% (64% CR). The median progression-free (PFS) and overall survival (OS) is 47.5 and 101.5 months. An international prognostic index score >1 was predictive for OS.

Conclusion

Myeloablative RIT with ¹³¹I-rituximab followed by ASCT is feasible, well-tolerated and effective in high risk CD20+ NHL. Combination of RIT and high-dose chemotherapy increased toxicity significantly. Long-term results for PFS and OS are encouraging.     

Health‐Related Quality of Life With Adjuvant Docetaxel‐ and Trastuzumab‐Based Regimens in Patients with Node‐Positive and High‐Risk Node‐Negative,HER2‐Positive Early Breast Cancer: Results from the BCIRG 006 Study

Background.

This study aims to describe and compare health-related quality of life (HRQL) in patients with node-positive and high-risk node-negative HER2-positive early breast cancer receiving adjuvant docetaxel and trastuzumab-based or docetaxel-based regimens alone.

Methods.

Eligible patients (n = 3,222) were randomly assigned to either four cycles of adjuvant doxorubicin and cyclophosphamide followed by four cycles of docetaxel (AC→T) or one of two trastuzumab-containing regimens: adjuvant doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab administered for 1 year (AC→TH) or six cycles of docetaxel plus carboplatin combined with trastuzumab administered for 1 year (TCH). The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and BR-23 were administered at baseline, the start of cycle 4 (mid), and the end of chemotherapy (EOC), as well as at 6, 12, and 24 months after chemotherapy.

Results.

Compliance rates for the EORTC questionnaires were acceptable at 72%–93% of eligible patients out to the 12-month assessment. Systemic side effect (SE) change scores were significantly improved for TCH-treated patients compared with AC→TH and AC→T at EOC, suggesting improved tolerability. Physical functioning (PF) was only slightly worse at midpoint for those receiving TCH, compared with patients who were just starting on taxane in an AC→TH regimen, but was otherwise similar between arms. All treatment arms recovered from the deterioration in SE, PF, and Global Health Scale scores by 1 year and median future perspective change scores continued to improve throughout treatment and follow-up.

Conclusion.

HRQL outcomes for adjuvant docetaxel and trastuzumab-based regimens are favorable and support TCH as a more tolerable treatment option.     

A Phase II Study of FOLFOXIRI Plus Panitumumab Followed by Evaluation for Resection in Patients With Metastatic KRAS Wild‐Type Colorectal Cancer With Liver Metastases Only

Lessons Learned

• This regimen is a viable option for patients with liver-only metastatic colorectal cancer.
• Enrollment criteria for future studies should include testing for the newly identified KRAS mutations.

Background.

Patients with liver-only metastatic colorectal cancer (mCRC) who are not candidates for potentially curative resection may become resectable with more aggressive chemotherapy regimens. In this nonrandomized trial, we evaluated folinic acid, 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) plus the epidermal growth factor receptor inhibitor panitumumab as first-line treatment for KRAS wild-type mCRC with liver-only metastasis.

Methods.

Patients received FOLFOXIRI (5-FU, 3,200 mg/m², 48-hour continuous intravenous (i.v.) infusion; leucovorin, 200 mg/m² i.v.; irinotecan, 125 mg/m²; oxaliplatin, 85 mg/m² i.v.) and panitumumab (6 mg/kg i.v.) on day 1 of 14-day cycles. Patients were restaged and evaluated for surgery every four cycles. Planned enrollment was originally 49 patients. The primary endpoint was objective response rate.

Results.

Fifteen patients (median age: 55 years; 87% male) received a median 6 cycles of treatment (range: 1–33 cycles); 10 patients (67%) were surgical candidates at baseline. Twelve patients were evaluable for clinical response; 9 (60%) achieved partial response. Ten patients underwent surgery; all had complete resections and pathologic partial response. Treatment-related grade 3 adverse events included diarrhea (33%) and rash (20%). Enrollment was halted because of emerging data on expanded KRAS/NRAS mutations beyond the region we initially examined, and the potential for negative interaction with oxaliplatin-based therapy. Eight patients underwent expanded KRAS/NRAS analysis outside exon 2; no additional mutations were found.

Conclusion.

KRAS/NRAS mutations outside the region tested in this study were recently shown to be associated with inferior survival on similar treatment regimens. Therefore, this trial was stopped early. This regimen remains a viable option for patients with liver-only mCRC in the KRAS/NRAS wild-type population. Enrollment criteria on future studies should include testing for the newly identified mutations.     

Brentuximab Vedotin in Transplant‐Naïve Relapsed/Refractory Hodgkin Lymphoma: Experience in 30 Patients

Background.

Hodgkin lymphoma (HL) is characterized by the presence of CD30-positive Hodgkin Reed-Sternberg cells. Approximately 30%–40% of patients with advanced disease are refractory to frontline therapy or will relapse after first-line treatment. The standard management of these patients is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT). The best prognostic factor is the status of disease before ASCT; in particular, the normalization of positron emission tomography (PET) scan. Brentuximab vedotin (BV) has shown a high overall response rate in refractory/relapsed HL after ASCT, whereas few data are available regarding its role before ASCT.

Patients and Methods.

A multicenter, retrospective, observational study was conducted. The primary endpoint of the study was the effectiveness of BV as single agent in patients with relapsed/refractory, ASCT-naïve HL, determined by the conversion of PET status from positive to negative; secondary endpoints were safety, capacity to proceed to ASCT, survival, and progression-free status.

Results.

Thirty patients with relapsed/refractory HL- and PET-positive disease after conventional chemotherapy salvage treatments were treated with a median of 4 cycles of BV. Normalization of PET findings (Deauville score ≤2) occurred in 9 of 30 patients (30%). Those nine patients proceeded to ASCT.

Conclusion.

These data suggest that BV can normalize PET status in a subset of HL patients refractory to conventional chemotherapy salvage treatments, such as ifosfamide-containing regimens, cytarabine- and platinum-containing regimens, prior to ASCT.

Implications for Practice:

Administration of brentuximab vedotin has resulted in a high overall response rate in refractory/relapsed Hodgkin lymphoma after autologous stem cell transplant, whereas few data are available regarding its role before transplant. The data suggest that brentuximab vedotin can normalize positron emission tomography results in a subset of patients refractory to conventional salvage treatments prior to transplant. Experience indicates that patients previously regarded as not ideal candidates for transplantation may be able to undergo further cytoreductive therapy using brentuximab vedotin.     

Treatment decisions and survival for people with small-cell lung cancer

Background:

Chemotherapy improves survival for many patients with SCLC, and hence it is important to understand variations in practice and outcomes for this treatment strategy.

Methods:

We used the National Lung Cancer Audit and Hospital Episodes Statistics to determine the proportion of patients who received chemotherapy for SCLC, and assess the effects of patient and organisational factors on the odds of receiving chemotherapy and of completing four cycles. We calculated median survival and used Cox regression to determine factors that predicted survival.

Results:

Of 15 091 cases of SCLC, 70% received at least one cycle of chemotherapy. More deprived people were less likely to receive chemotherapy, but patients were more likely to receive chemotherapy, and to complete ⩾four cycles, if they were referred to the lung cancer team by their GP. Median survival for those treated with chemotherapy was 12.9 months for limited and 7.3 months for extensive stage disease.

Conclusions:

The Linked NLCA and HES data provide real-life measures of survival in people treated with chemotherapy and show how this is influenced by patient and tumour characteristics. These data show the characteristics of patients who are less likely to complete a full course of treatment, an adverse predictor of survival.     

A Phase II Study of Ifosfamide,Methotrexate, Etoposide,and Prednisolone for Previously Untreated Stage I/II Extranodal Natural Killer/T‐Cell Lymphoma,Nasal Type: A Multicenter Trial of the Korean Cancer Study Group

Background.

Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL).

Methods.

Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m² on days 1–3; methotrextate 30 mg/m² on days 3 and 10; etoposide 100 mg/m² on days 1–3; and prednisolone 60 mg/m² per day on days 1–5) followed by involved field radiotherapy (IFRT).

Results.

Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively.

Conclusion.

Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL.     

Epidermal Growth Factor Receptor (EGFR)‐Tyrosine Kinase Inhibitor Treatment and Salvage Chemotherapy in EGFR‐Mutated Elderly Pulmonary Adenocarcinoma Patients

Background.

Lung cancer is frequently a disease of elderly patients. However, these patients are often treated less actively owing to a higher comorbidity rate and poor performance status. The efficacy of different treatments in elderly patients with epidermal growth factor receptor (EGFR)-mutated lung cancer is still unknown.

Materials and Methods.

We retrospectively reviewed the records of our pulmonary adenocarcinoma patients treated between 2010 and 2013. Data on patient age, type of tumor EGFR mutation, response to first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, type of salvage chemotherapy, and efficacy of EGFR-TKI and salvage chemotherapy were collected.

Results.

In all, 473 of 1,230 stage IV adenocarcinoma patients had an EGFR mutation, and 330 of them received first-line TKI treatment. Of the 330 patients, 160 were ≥70 years old (elderly group) and 170 were <70 years old (younger group). The response rate and progression-free survival (PFS) with first-line TKI treatment were not significantly different. The elderly group had shorter median survival. A total of 107 patients received salvage chemotherapy after first-line EGFR-TKI treatment: 45 in the elderly group and 62 in the younger group. Their response rate and PFS were not significantly different; however, the younger group had longer median survival. Additional subgroup analysis showed that younger patients who received platinum-based chemotherapy or combination chemotherapy had better median survival than did the elderly patients. The PFS was longer among younger patients receiving a platinum-based regimen than that among the elderly patients.

Conclusion.

Elderly patients with disease progression after first-line EGFR-TKI treatment can receive chemotherapy and have a response rate similar to that of younger patients.

Implications for Practice:

The aim of the present study was to investigate the efficacy of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in elderly patients and the outcomes of subsequent salvage chemotherapy after disease progression. The most important finding was that elderly patients with disease progression after first-line EGFR-TKI treatment can receive salvage chemotherapy and have a response rate similar to that of younger patients who received salvage chemotherapy.     

A phase II trial of dose-dense chemotherapy,followed by surgical resection and/or thoracic radiotherapy,in locally advanced thymoma: report of a Japan Clinical Oncology Group trial (JCOG 9606)

Background:

This study aimed to evaluate the safety and efficacy of dose-dense weekly chemotherapy, followed by resection and/or thoracic radiotherapy.

Methods:

Patients with histologically documented thymoma with unresectable stage III disease received 9 weeks of chemotherapy: cisplatin 25 mg m⁻² on weeks 1–9; vincristine 1 mg m⁻² on weeks 1, 2, 4, 6 and 8; and doxorubicin 40 mg m⁻² and etoposide 80 mg m⁻² on days 1–3 of weeks 1, 3, 5, 7 and 9. Patients went on to surgery and post-operative radiotherapy of 48 Gy; those with unresectable disease received 60 Gy radiotherapy.

Results:

total of 23 patients were entered. The main toxicities of the chemotherapy regimen were neutropenia and anaemia, and 57% of patients completed the planned 9 weeks of therapy. There were no toxic deaths. Of the 21 eligible patients, 13 (62%) achieved a partial response (95% confidence interval: 38–82%). Thirteen patients underwent a thoracotomy and nine (39%) underwent complete resection. Progression-free survival at 2 and 5 years was 80 and 43%, respectively. Overall survival at 5 and 8 years was 85 and 69%, respectively. Survival did not seem to be affected by resection.

Conclusion:

In thymoma patients, weekly dose-dense chemotherapy has activity similar to that of conventional regimens. Although some patients could achieve complete resection, the role of surgery remains unclear.     

Phase I/II Study of Weekly Oraxol for the Second‐Line Treatment of Patients With Metastatic or Recurrent Gastric Cancer

Lessons Learned

• Oraxol, a novel oral formulation of paclitaxel, displayed modest efficacy as second-line chemotherapy for gastric cancer.
• Considering its favorable toxicity profiles, further studies are warranted in various solid tumors including gastric cancer.

Background.

Oraxol consists of paclitaxel and HM30181A, a P-glycoprotein inhibitor, to increase the oral bioavailability of paclitaxel. This phase I/II study (HM-OXL-201) was conducted to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of Oraxol. In addition, we investigated the efficacy and safety of Oraxol as second-line chemotherapy for metastatic or recurrent gastric cancer (GC).

Methods.

In the phase I component, paclitaxel was orally administered at escalating doses (90, 120, or 150 mg/m² per day) with a fixed dose (15 mg/day) of HM30181A. Oraxol was administrated 6 times per cycle (days 1, 2, 8, 9, 15, and 16) every 4 weeks. In the phase II component, the efficacy and safety of Oraxol were evaluated.

Results.

In the phase I component, the MTD could not be determined. Based on toxicity and pharmacokinetic data, the RP2D of oral paclitaxel was determined to be 150 mg/m². In the phase II component, 4 of 43 patients (9.3%) achieved partial responses. Median progression-free survival and overall survival were 2.6 and 10.7 months, respectively. Toxicity profiles were favorable, and the most common drug-related adverse events (grade ≥3) were neutropenia and diarrhea.

Conclusion.

Oraxol exhibited modest efficacy and favorable toxicity profiles as second-line chemotherapy for GC.     

Survival Following Surgery with or without Adjuvant Chemotherapy for Stage I–IIIA Non‐Small Cell Lung Cancer: An East Asian Population‐Based Study

Background.

Asian ethnicity is associated with a distinct molecular etiology, treatment response, and survival outcome among patients with non-small cell lung cancer (NSCLC). This study examines the survival impact of platinum-based adjuvant chemotherapy for Asian patients with stage I–IIIA NSCLC.

Methods.

This study recruited patients aged ≥18 years with histologically proven stage IA–IIIA NSCLC registered in the Taiwan Cancer Registry database in January 2004 to December 2007. Platinum-containing adjuvant chemotherapy had to be started within 90 days of the primary surgery. Kaplan–Meier survival curves, log-rank tests, and the Cox proportional hazards regression model were used to assess the influence of various risk factors on survival time.

Results.

This study included 2,231 patients with stage IA–IIIA NSCLC who underwent primary surgery with a clear surgical margin. The percentages of all causes of death were significantly lower for the chemotherapy group for both stage II and stage IIIA patients. Multivariate analysis identified platinum-based adjuvant chemotherapy as an independent prognostic factor for the overall survival outcome of stage II (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.39–0.94; p = .024) and IIIA (HR, 0.71; 95% CI, 0.52–0.96; p = .029) patients. Among these patients, those who received adjuvant chemotherapy had a superior overall survival outcome for both genders, for the subgroup of patients aged ≥70 years, and for those with adenocarcinoma.

Conclusion.

Platinum-based adjuvant chemotherapy should be considered in the treatment plan for Asian patients with resected stage II and stage IIIA NSCLC.     

FOLFOX‐4 Chemotherapy for Patients With Unresectable or Relapsed Peritoneal Pseudomyxoma

Purpose.

The standard treatment of peritoneal pseudomyxoma is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma. The aim of our study was to assess the activity of chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX-4 regimen) in terms of response rate in this subset of patients.

Materials and Methods.

Patients were included in a single-center, observational study and treated with FOLFOX-4 administered every 2 weeks for up to 12 cycles or until progressive disease or unacceptable toxicity.

Results.

Twenty consecutive patients were reviewed from July 2011 to September 2013. Only partial responses were observed, with an objective response rate of 20%. Median progression-free survival and overall survival were 8 months and 26 months, respectively. Two patients were able to undergo laparotomy with complete cytoreduction and HIPEC in one case. Safety data for FOLFOX-4 were consistent with the literature. By means of a mutant enriched polymerase chain reaction, KRAS mutation was found in 16 of 19 cases (84%), and MGMT promoter methylation was found in 8 (42%, all KRAS mutant).

Conclusion.

FOLFOX-4 chemotherapy is tolerable and active in patients with peritoneal pseudomyxoma when disease is deemed unresectable or relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers, such as KRAS for resistance to anti-epidermal growth factor receptor monoclonal antibodies and MGMT for response to temozolomide, is a priority for the development of evidence-based treatment strategies for peritoneal pseudomyxoma.     

Oxaliplatin-dacarbazine combination chemotherapy for the treatment of advanced soft tissue sarcoma of the limbs

Background

This study was designed to explore the feasibility, safety, and outcomes of pre-operative oxaliplatin-dacarbazine combination therapy for the treatment of advanced soft tissue sarcoma (STS) of the limb.

Patients and Methods

Between November 2005 and November 2008, 31 patients with advanced limb STS classified with stage IV STS were randomly assigned into experimental or control groups, and both were given 2 cycles of chemotherapy before undergoing surgery. The regimen for the experimental group was oxaliplatin (120 mg/m², d₁) in combination with dacarbazine (175 mg/m², d_1-3), while that for the control group was a standard vincristine, epirubicin, cyclophosphamide therapy. Operations were carried out four weeks after the second chemotherapy cycle, followed by another 2-4 more chemotherapy cycles of the previous regimen.

Results

Following preoperative chemotherapy, the experimental group exhibited a significant improvement in tumor regression compared to controls. Both regimens were well-tolerated, and no significant differences in adverse reactions were noted. At a median follow-up of 24 months, 28 patients were still alive and had normal limb function. The progression free survival rate of the experimental group was significantly higher than that of the control group (10/15 vs. 4/16, p < 0.05).

Conclusion

Oxaliplatin- dacarbazine neoadjuvant/adjuvant chemotherapy improved the prognosis of patients with advanced limb STS in comparison with vincristine, epirubicin, cyclophosphamide combination therapy.