Maintenance Erlotinib Research Articles

A Phase II Trial of Erlotinib as Maintenance Treatment After Gemcitabine Plus Platinum-based Chemotherapy in Patients With Recurrent and/or Metastatic Nasopharyngeal Carcinoma

Despite the efficacy of gemcitabine-platinum regimen, the outcome of patients with recurrent and/or metastatic nasopharyngeal carcinoma (RM NPC) is poor. A phase II trial was conducted to determine the efficacy of erlotinib, given as maintenance therapy after gemcitabine-platinum chemotherapy in patients with RM NPC. Patients were treated with gemcitabine 1000 mg/m on days 1 and 8 as well as cisplatin 70 mg/m on day 1 (or carboplatin area under curve 5 on day 1, if contraindication to cisplatin) 3 weeks. After 6 chemotherapy cycles (or before in case of progression), patients were switched to erlotinib 150 mg/d 4 weeks. Primary end point was time to progression in patients without progressive disease after 6 chemotherapy cycles and treated with maintenance erlotinib. Epstein-Barr virus DNA plasma levels, measured using quantitative real-time polymerase chain reaction, were correlated with outcome. Of 20 enrolled patients, 19 patients received 96 chemotherapy cycles. Fifteen patients were switched to erlotinib and received 36 cycles (range: 1 to 6 cycles). Safety profiles observed with the chemotherapy combination and erlotinib were those expected. Of 12 patients evaluable for response to erlotinib, all progressed except 3 patients (25%) who had stable disease for 3, 4, and 7 months, respectively. Median time to progression was 6.9 months for 13 patients without progressive disease after 6 chemotherapy cycles and treated with erlotinib. No correlation was identified between Epstein-Barr virus DNA plasma levels and clinical outcome. Maintenance or second-line therapy with erlotinib after chemotherapy was not effective in RM NPC. Historical comparison with patients treated with the same chemotherapy alone until progression suggests that it may be detrimental to stop chemotherapy after 6 cycles if disease did not progress.

Efficacy of pemetrexed as second-line therapy in advanced NSCLC after either treatment-free interval or maintenance therapy with gemcitabine or erlotinib in IFCT-GFPC 05-02 phase III study.

7574 Background: Continuous exposure of tumor cells to maintenance therapy in advanced NSCLC might lead to resistance to subsequent treatments. IFCT–GFPC 0502 study showed a progression-free survival (PFS) benefit with gemcitabine (G) or erlotinib (E) maintenance compared to observation (O) after cisplatin-G induction chemotherapy. The trial included a pre-defined second-line therapy with pemetrexed (P), allowing post-hoc assessment of its efficacy according to previous maintenance treatment or treatment-free interval. Methods: Stage IIIB/IV NSCLC patients (pts) with a PS of 0-1 were randomized after 4 cycles of cisplatin-G chemotherapy to O or to receive maintenance therapy with G or E until disease progression. P was given as second-line treatment on disease progression in all arms. PFS and OS were assessed from the beginning of P therapy according to randomization arm. Tumor response to P and tolerance were also analyzed. Results: Of the 464 pts randomized to either O (155), G (154) or E (155), 360 pts (78 %) received P as second-line therapy, i.e. 130 (84%), 114 (74%) and 116 (75%) in O, G and E arm, respectively. Baseline characteristics remained well balanced between arms (overall median age of 58 years, 28% female, 91% stage IV, 41% PS 0, 65/19/16%, adenocarcinoma/squamous/other, 10% non-smokers and 56% responders to induction CT). Median number of delivered P cycles was 3 (1-40) in all arms. Response rate was 19%, 7% and 15% for non-squamous pts in O, G and E, respectively. Median PFS did not significantly differ between G and O (4.2 vs 3.9 months, HR [95% CI] 0.81 [0.62-1.06]) or E and O (4.2 vs 3.9 months, HR 0.83 [0.64-1.09]). OS data showed a non-significant improvement with G vs O (HR 0.81 [0.61-1.07]) or E vs O (HR 0.80 [0.61-1.05]), with a median of 7.5, 8.3 and 9.1 months for O, G and E, respectively. Results were similar when analysis was restricted to non-squamous pts. Grade 3-4 treatment-related AEs were similar in O (33.1%), G (31.6%) and E (25%). Conclusions: Maintenance therapy with continuation of G or switch to E does not impair the efficacy of second-line P by comparison with administration after a treatment-free interval.

A randomized placebo-controlled phase III study of intercalated erlotinib with gemcitabine/platinum in first-line advanced non-small cell lung cancer (NSCLC): FASTACT-II.

7519^ Background: FASTACT, a randomized, phase 2 study in advanced NSCLC, found that intercalated erlotinib with 1st-line platinum-based chemotherapy (CT) significantly prolongs progression-free survival (PFS) (HR 0.47, p=0.0002) versus CT alone (Mok et al. JCO 2009). FASTACT-II is a confirmatory, randomized, phase 3, placebo-controlled, double-blind study in a large patient population Methods: Patients with untreated stage IIIB/IV NSCLC and ECOG PS 0/1 were randomized (1:1) to receive up to 6 cycles of gemcitabine (1,250 mg/m2 on d1 and 8) plus platinum (carboplatin 5×AUC or cisplatin 75 mg/m2 on d1) q4w, with either intercalated erlotinib (150 mg/day on d15–28) or placebo. Non-progressing patients received maintenance erlotinib or placebo until progression, unacceptable toxicity or death. Stratification was by disease stage, histology, smoking status and CT regimen. Primary endpoint was PFS; secondary endpoints included overall response rate (ORR), overall survival (OS), safety, QoL and biomarker analyses. Results: From Apr 2009 to Sep 2010, 451 patients were randomized to receive erlotinib (n=226) or placebo (n=225). Baseline demographics were well balanced across the arms; overall, 49% were never smokers, 40% were female and 76% had adenocarcinoma. PFS was significantly prolonged with erlotinib vs placebo: median 7.6 vs 6.0 months, respectively; HR 0.57 (95% CI 0.46–0.70); p<0.0001. ORR was significantly improved with erlotinib vs placebo: 42.9% vs 17.8%; p<0.0001. A non-significant trend towards longer OS was seen with erlotinib vs placebo (median 18.3 vs 14.9 months; HR 0.78 [95% CI 0.60–1.02]; p=0.069); 73% of placebo patients received a 2nd-line EGFR TKI. Except for skin rash with erlotinib, there was no clinically significant difference in toxicity between arms. A total of 283 patients (62.7%) provided samples for biomarker analyses, including EGFR mutation status, results of which will be presented. Conclusions: Intercalation of erlotinib with CT significantly prolonged PFS in 1st-line advanced NSCLC. Biomarker analysis will determine the significance of this regimen in patients with or without activating EGFR mutations.

Cost-utility analysis of maintenance therapy with either gemcitabine or erlotinib versus observation with predefined second-line treatment after cisplatin-gemcitabine induction chemotherapy in advanced NSCLC: IFCT-GFPC 0502-eco phase III study.

e16560 Background: The IFCT–GFPC 0502 phase III study reported a prolongation of progression-free survival with maintenance with either gemcitabine or erlotinib versus observation after cisplatin-gemcitabine induction chemotherapy in advanced NSCLC. The aim of this analysis is to assess the incremental cost-effectiveness ratio (ICER) of these strategies in the global population and in pre specified sub-groups. Methods: A cost-utility analysis was performed to evaluate ICER of maintenance therapy with either gemcitabine or erlotinib, compared to observation, from randomization until end of follow up. Direct medical costs (including drugs costs, hospitalization, follow-up examinations, second-line treatment and palliative costs) were prospectively collected per patient alongside the trial, until death, from the third party payer perspective. Utility data were extracted from literature. Sensitivity analyses were performed. Results: The ICER for maintenance therapy with gemcitabine and erlotinib were respectively 84,011 and 183,261 euros per quality-adjusted life years (QALY). Gemcitabine maintenance therapy had a favourable ICER in patients with PS = 0 (51,168 €/Qaly), in responders to induction chemotherapy (65,554€/Qaly) and in patients with squamous cell carcinoma (44,884€/Qaly); erlotinib had a favourable ICER in patients with PS = 0 (162,371 €/Qaly) and objective response to induction (101,569 €/Qaly ). Conclusions: Gemcitabine and erlotinib maintenance therapy have acceptable ICER but with a wide variation function of histology, PS and response to the first line chemotherapy.

Selection of chemotherapy for patients with advanced non–small cell lung cancer

Chemotherapy remains the first-line treatment for most patients with stage IV non-small cell lung cancer (NSCLC), but optimal regimens are now defined by histology. Platinum-based regimens with pemetrexed, bevacizumab, or both are reasonable first-line options for patients with nonsquamous NSCLC. The standard treatment for squamous NSCLC remains a platinum doublet with a drug other than pemetrexed. Maintenance therapy is emerging as a treatment strategy for patients who do not progress after four cycles of first-line chemotherapy. In the maintenance setting, pemetrexed and erlotinib significantly prolong overall survival compared with placebo after the completion of first-line chemotherapy.

Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: A subanalysis of the phase III, randomized SATURN study

Maintenance therapy, commenced immediately after the completion of first-line chemotherapy, is a promising strategy for improving treatment outcomes in patients with non-small-cell lung cancer (NSCLC). The global phase III SequentiAl Tarceva in UnResectable NSCLC (SATURN) study evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib as maintenance treatment in NSCLC patients without progression after first-line chemotherapy. We report a retrospective subanalysis of Asian patients enrolled in SATURN.Patients with advanced NSCLC with no evidence of progression after four cycles of chemotherapy were randomized to receive erlotinib 150mg/day or placebo, until progressive disease or limiting toxicity. The co-primary endpoints of SATURN were progression-free survival (PFS) in all patients and in those with positive EGFR immunohistochemistry (IHC) status. Secondary endpoints included overall survival (OS), disease control rate, safety, quality of life (QoL) and biomarker analyses.In total, 126 patients from East and South-East Asian centers were randomized (14% of the intent-to-treat population): 88 from Korea, 28 from China and 10 from Malaysia; one patient was excluded from this analysis due to Indian ethnicity. PFS was significantly prolonged in the erlotinib treatment arm, both overall (hazard ratio [HR]: 0.57; p=0.0067) and in patients with EGFR IHC-positive disease (HR=0.50; p=0.0057). There was a trend towards an increase in OS, which reached statistical significance in the EGFR IHC-positive subgroup (p=0.0233). The overall response rate was significantly higher with erlotinib compared with placebo (24% versus 5%; p=0.0025). Erlotinib was generally well tolerated and had no negative impact on QoL in this subpopulation. The most common treatment-related adverse events were rash, diarrhea and pruritus.Erlotinib was effective and well tolerated in Asian patients, producing benefits consistent with those observed in the overall SATURN population. Maintenance treatment with erlotinib appears to be a useful option for the management of Asian patients with advanced NSCLC without progression after first-line chemotherapy.

Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy

In the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC). After four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]). Following first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR; <1% unknown response). Erlotinib maintenance therapy significantly prolonged PFS in both the SD (hazard ratio [HR] = 0.68; P < 0.0001) and CR/PR (HR = 0.74; P = 0.0059) groups, while OS was significantly prolonged in the SD group only (HR = 0.72; P = 0.0019). The erlotinib-related OS benefit in the SD group remained significant across subgroups, irrespective of tumour histology and/or EGFR mutation status. The incidence of adverse events was similar in the SD group and the overall population, and erlotinib treatment did not negatively impact quality of life. Patients with advanced NSCLC and SD following first-line platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy.

Prospective Molecular Marker Analyses of EGFR and KRAS From a Randomized, Placebo-Controlled Study of Erlotinib Maintenance Therapy in Advanced Non–Small-Cell Lung Cancer

Prospective Molecular Marker Analyses of EGFR and KRAS From a Randomized, Placebo-Controlled Study of Erlotinib Maintenance Therapy in Advanced Non–Small-Cell Lung Cancer

Prospective Molecular Marker Analyses of EGFR and KRAS From a Randomized, Placebo-Controlled Study of Erlotinib Maintenance Therapy in Advanced Non–Small-Cell Lung Cancer

Prospective Molecular Marker Analyses of EGFR and KRAS From a Randomized, Placebo-Controlled Study of Erlotinib Maintenance Therapy in Advanced Non–Small-Cell Lung Cancer

Targeted and Cytotoxic Therapy in Coordinated Sequence (TACTICS): Erlotinib, Bevacizumab, and Standard Chemotherapy for Non–Small-Cell Lung Cancer, A Phase II Trial

BackgroundThis trial focused on optimally combining existing targeted therapies and cytotoxic chemotherapy in the treatment of unselected patients with advanced non–small-cell lung cancer (NSCLC). MethodsPatients with previously untreated advanced-stage nonsquamous NSCLC were eligible for this trial. In module A, patients received up to 4 cycles of erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks. Patients then received carboplatin (AUC = 6), paclitaxel 200 mg/m2, and bevacizumab 15 mg/kg for 4 cycles in module B. Patients who did not have progressive disease in module A received maintenance erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks in module C. ResultsForty-eight patients were enrolled in this multicenter phase II trial. Most patients were male (62.5%) and white (77.1%) with stage IV disease (93.8%) and adenocarcinoma histologic type (66.7%). The overall response rate in module A was 10.4%, in module B it was 15.1%, and in module C it was 5.5%. The study achieved its primary endpoint, with a nonprogression rate of 45.8% in module A. The median overall survival (OS) was 12.6 months. ConclusionThe novel systemic therapy regimen is feasible in patients with advanced NSCLC. However there is no further role for developing this regimen in unselected patients with NSCLC.

Erlotinib as maintenance therapy in patients with advanced non-small cell lung cancer

Three randomized trials (SATURN, ATLAS and IFCT-GFPC 0502) have demonstrated that the oral antiepidermal growth factor receptor tyrosine kinase inhibitor erlotinib can improve progression-free survival (PFS) and overall survival (OS), as maintenance therapy after first-line chemotherapy in advanced non-small cell lung cancer. We pooled the results of these three trials by performing a meta-analysis of hazard ratios (HRs) and the 95% confidence intervals (CIs) for the PFS and the OS for maintenance erlotinib versus observation, standard therapy or placebo. The benefits in the predefined subgroups of patients [according to histology, sex, performance status (PS), and smoking status] were assessed. The OS was superior in the 963 patients treated with erlotinib than in the 979 nontreated patients [HR=0.87 (P=0.003), corresponding to a 13% reduction in the risk of death. The pooled HR for the PFS is 0.76 (P<0.00001), corresponding to a 24% lower risk of being progression free]. All the patients in the subgroup analysis experienced a benefit from erlotinib and, in particular, never-smoking women with nonsquamous histology with a PS of 0. Both responders and those with stable disease obtain PFS benefit. The addition of maintenance erlotinib significantly improves PFS and OS in patients with advanced non-small cell lung cancer who had not progressed after four cycles of first-line chemotherapy. The benefit does not seem to be limited to a particular subgroup, although it is more pronounced in never-smoking women patients with nonsquamous carriers with a PS of 0.

Prospective Molecular Marker Analyses of EGFR and KRAS From a Randomized, Placebo-Controlled Study of Erlotinib Maintenance Therapy in Advanced Non–Small-Cell Lung Cancer

The phase III, randomized, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study found that erlotinib maintenance therapy extended progression-free survival (PFS) and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) who had nonprogressive disease following first-line platinum-doublet chemotherapy. This study included prospective analysis of the prognostic and predictive value of several biomarkers. Mandatory diagnostic tumor specimens were collected before initiating first-line chemotherapy and were tested for epidermal growth factor receptor (EGFR) protein expression by using immunohistochemistry (IHC), EGFR gene copy number by using fluorescent in situ hybridization (FISH), and EGFR and KRAS mutations by using DNA sequencing. An EGFR CA simple sequence repeat in intron 1 (CA-SSR1) polymorphism was evaluated in blood. All 889 randomly assigned patients provided tumor samples. EGFR IHC, EGFR FISH, KRAS mutation, and EGFR CA-SSR1 repeat length status were not predictive for erlotinib efficacy. A profound predictive effect on PFS of erlotinib relative to placebo was observed in the EGFR mutation-positive subgroup (hazard ratio [HR], 0.10; P < .001). Significant PFS benefits were also observed with erlotinib in the wild-type EGFR subgroup (HR, 0.78; P = .0185). KRAS mutation status was a significant negative prognostic factor for PFS. This large prospective biomarker study found that patients with activating EGFR mutations derive the greatest PFS benefit from erlotinib maintenance therapy. No other biomarkers were predictive for outcomes with erlotinib, although the study was not powered for clinical outcomes in biomarker subgroups other than EGFR IHC-positive [corrected]. KRAS mutations were prognostic for reduced PFS. The study demonstrated the feasibility of prospective tissue collection for biomarker analyses in NSCLC.

First-line erlotinib maintenance cost effective in Europe

First-line erlotinib maintenance cost effective in Europe

Erlotinib beyond progression study: Randomized phase II study comparing chemotherapy plus erlotinib with chemotherapy alone in EGFR TKI-responsive, advanced non-small cell lung cancer (NSCLC) that subsequently progresses.

TPS211 Background: EGFR-driven NSCLCs are dependent on the EGFR pathway for proliferation which EGFR TKIs potently block. Progression occurs when resistance to erlotinib develops—through the emergence of EGFR—T790M or MET gene amplification. This event is likely specific to any given individual tumor clone and therefore on relapse only some tumor clones carry resistance mutations, others likely remain dormant while the EGFR pathway is inhibited providing rationale for maintenance therapy. This concept is supported by clinical observations demonstrating of “tumor flares” in patients taken off of EGFR TKI therapy on progression. Similar analogies exist in prostate cancer/maintenance of castrate state, breast cancer/maintenance trastuzumab. This study seeks preliminary evidence that such a strategy can lead to meaningful benefits in advanced non-small cell lung cancer. Methods: Randomized, phase II study of pemetrexed chemotherapy versus pemetrexed chemotherapy plus erlotinib in patients who derived a clinical benefit from erlotinib but now have evidence of progressive disease (NCT00660816). Pemetrexed is given at standard dose of 500 mg/m2 every 3 weeks to a maximum of 8 cycles while erlotinib is given at 150 mg oral daily dose on days 2-19 of each cycle. Our main hypothesis is that maintenance erlotinib in this patient population could extend PFS by 50%, from 3 to 4.5 months and we seek to enroll 78 patients by randomized phase II screening design to allow 80% power to detect such a difference. Standard eligibility criteria include progression following at least twelve weeks of treatment with single-agent erlotinib during which time the patients experienced a clinical benefit. 23 of planned 78 patients have been enrolled and current enrollment averages 1-2 new patients per month. An amendment to allow either pemetrexed or docetaxel as the chemotherapy base is under review to further enhance accrual. Translational studies, including EGFR and other gene mutation analyses will also be performed.

Pancreatic adenocarcinoma-associated polymyositis treated with corticosteroids along with cancer specific treatment: case report

BackgroundAdenocarcinoma of the pancreas only rarely is associated with inflammatory myopathy. In this setting, polymyositis may be treated with glucocorticoids in combination with cancer specific treatment.Case presentationWe present the case of a 52-year-old man with stage IIA pancreatic tail adenocarcinoma who underwent surgical treatment and six months into therapy with gemcitabine he developed symmetrical, painful, proximal muscle weakness with peripheral oedema. Re-evaluation with imaging modalities, muscle histology and biochemistry conferred the diagnosis of polymyositis associated with pancreatic cancer progression. The patient was treated with glucocorticoids along with gemcitabine and erlotinib which resulted in complete remission within six months. He remained in good health for a further six months on erlotinib maintenance therapy when a new computer tomography scan showed pancreatic cancer relapse and hence prompted 2nd line chemotherapy with gemcitabine.ConclusionsPolymyositis associated with pancreatic cancer may respond to glucocorticoids along with cancer specific treatment.

Targeted Therapies and other Agents as First-Line Maintenance and Beyond: Particular Benefit in Pulmonary Adenocarcinoma Patients

As of today, advanced non-small cell lung cancer is still an incurable disease. However, recent researches on the biology of adenocarcinoma have led to considerable progress in the treatment of this subgroup of patients. The administration of bevacizumab and pemetrexed as first-line therapy, erlotinib in the maintenance phase and erlotinib again combined with vandetanib as second-line therapy, gives patients with lung adenocarcinoma new hope. In particular, in metastatic adenocarcinoma with an EML4-ALK fusion oncogene, crizotinib (a selective, ATP-competitive, small molecule, orally bioavailable inhibitor of the ALK and MET/HGF receptor tyrosine kinases), led to a response rate of 64%, which is similar to the results achieved in chronic myeloid leukemia and GIST with imatinib. Overall, the application of all available active therapies during the natural history of adenocarcinoma may lead to a survival benefit that was unimaginable only a few years ago. This article reviews the main studies on molecular targeted therapies in various lines of treatment of advanced lung adenocarcinoma.

88PD EFFICACY AND SAFETY OF ERLOTINIB VERSUS CHEMOTHERAPY IN SECOND-LINE ADVANCED NON-SMALL-CELL LUNG CANCER (NSCLC) WITH POOR PROGNOSIS: THE PHASE III TITAN STUDY

Background: Erlotinib (E), docetaxel (D) and pemetrexed (P) are all approved in the second-line setting for patients (pts) with advanced NSCLC who progress following first-line platinum doublet chemotherapy (PDC), but head-to-head data from large clinical trials are limited. The multicentre, international, openlabel, phase III TITAN study investigated the efficacy and tolerability of E vs chemotherapy (D or P) as second-line therapy for NSCLC after rapid progression on first-line PDC. Methods: During initiation, 2590 chemonaive pts with advanced NSCLC received up to 4 cycles of first-line PDC. Pts with controlled disease were offered entry into the SATURN phase III study of maintenance erlotinib; those with disease progression were offered entry into TITAN (n = 424). Pts in TITAN were stratified by stage, ECOG PS, smoking history and region, and were randomised (1:1) to receive E 150mg/d or chemotherapy (either D or P, investigators’ choice; standard regimens), until toxicity or progression. Overall survival (OS) was the primary endpoint. Secondary endpoints included progression-free survival (PFS), response rate (ORR), biomarker analyses and safety. Results: Baseline characteristics were balanced between the two arms and the full analysis population comprised 203 pts for E and 221 for chemotherapy (116 for D and 105 for P). No difference in OS was seen between arms: HR = 0.96 (95% CI 0.78 1.19; log-rank p = 0.73; median 5.3 months with E vs 5.5 months with chemotherapy). Similarly, no significant difference was seen in PFS: HR = 1.19 (95% CI 0.97 1.46; log-rank p = 0.09; median 6.3 weeks with E vs 8.6 weeks with chemotherapy). Subgroup analyses will be presented. ORR was 7.9% with E vs 6.3% with chemotherapy. More treatmentrelated adverse events were seen with E (AEs; 58.2% vs 40.8% with chemotherapy), mostly grade 1/2 rash or diarrhoea. Grade 5 AEs were rare with E (1.5% vs 5.2% of pts on chemotherapy). Serious treatment-related AEs were seen in 1% of pts in the E arm vs 6.6% of those in the chemotherapy arm; withdrawal due to AEs was required in 1% and 3.8% of pts, respectively. Conclusions: Erlotinib had similar efficacy to chemotherapy in second-line advanced NSCLC, even in patients who had progressed rapidly on first-line PDC. Erlotinib was well tolerated compared with chemotherapy in this population. Disclosure: T. Ciuleanu: I have taken part in Advisory boards for Roche, Amgen, Merck, GlaxoSmithKline, Lilly, BMS, OSIP. All other authors have declared no conflicts of interest.

Phase 1 trial of concurrent erlotinib, celecoxib, and reirradiation for recurrent head and neck cancer

Concurrent inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) is an active and well tolerated regimen in recurrent head and neck cancer (HNC). In the current phase 1 trial, the authors sought to determine the maximum tolerated dose (MTD) and efficacy of concurrent erlotinib and celecoxib as a radiosensitizing regimen. Fourteen patients with previously irradiated HNC with no distant metastases who required reirradiation were eligible. Treatment consisted of daily erlotinib 150 mg and twice daily celecoxib (escalated from 200 mg to 600 mg using a 3 + 3 design with an expanded cohort at the MTD) starting on Day 1 and was continued during radiation. Daily radiation was started on Day 15, and maintenance erlotinib was recommended. The recommended phase 2 dose of celecoxib was 400 mg. Three dose-limiting toxicities included late in-field orocutaneous fistula (Dose Level 2), osteonecrosis (Dose Level 3), and trismus (Dose Level 3). Acute grade ≥ 3 toxicities were uncommon and included mucositis (21%) and dermatitis (14%). At a median follow-up of 11 months, the 1-year locoregional control, progression-free survival, and overall survival rates were 60%, 37%, and 55%, respectively. Concurrent erlotinib, celecoxib, and reirradiation was a feasible and clinically active regimen in a population of patients with recurrent HNC who had a poor prognosis.

Best of the Month: A Round Up of Articles Published in Recent Months

With the abundant number of articles published in lung cancer, it has become very difficult to stay updated. After a search through variety of medical journal for articles published between March and June 2010, we selected the studies considered to have the greatest relevance for oncologists involved in the treatment of lung cancer. The nine selected studies covered a broad range of topics including possible hormonal role in the development of lung adenocarcinoma, lung cancer in never smokers, stereotactic radiotherapy for early-stage lung cancer, prognostic role of pleural lavage cytology, neoadjuvant chemotherapy for operable lung cancer, maintenance erlotinib, use of erlotinib after gefitinib, comparison of the two epidermal growth factor receptor tyrosine kinase inhibitors, and risk of central nervous system relapse in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors.

The SATURN Trial: The Value of Maintenance Erlotinib in Patients with Non-Small-Cell Lung Cancer

The first-line treatment of advanced non-small-cell lung cancer (NSCLC) generally consists of a maximum of six cycles of platinum-based doublet chemotherapy followed by surveillance for disease progression. Recently, the strategy of starting second-line treatment immediately following the completion of chemotherapy, known as 'maintenance' chemotherapy, has been investigated. The use of maintenance pemetrexed improves both progression-free and overall survival, while the use of maintenance docetaxel did not significantly improve overall survival. The Sequential Tarceva in Unresectable NSCLC (SATURN) study investigated the use of maintenance erlotinib following the completion of first-line chemotherapy. It demonstrated a significant improvement in overall survival from 11.1 months in the placebo group to 12.3 months in patients receiving maintenance erlotinib, with the important caveat that only 21% of patients in the placebo group ever received erlotinib. A subset of patients whose tumors had EGF receptor mutations had a higher magnitude of benefit from maintenance treatment. Therefore, maintenance erlotinib should be considered in the treatment of patients with NSCLC.