A Phase II Study of Irinotecan for Patients with Previously Treated Small-Cell Lung Cancer.

OBJECTIVE: Chemotherapy with irinotecan plus cisplatin has shown promise in chemo-naïve small-cell lung cancer (SCLC) patients. However, irinotecan treatment for relapsed or refractory SCLC has not been adequately evaluated. This phase II study evaluated the appropriate treatment schedule of irinotecan as a single agent. This study was designed to determine the antitumor activity, toxicity, and survival in previously treated SCLC patients. METHODS: Previously treated SCLC patients with at least one platinum-based regimen received irinotecan (100 mg/m2) on days 1 and 8, every 3 weeks, until disease progression. The assessment of the response rate was the primary endpoint. RESULTS: Thirty patients were enrolled, with an objective response rate of 41.3% (95% confidence interval [CI] 25.5-59.3), and a disease control rate of 69%. Median progression-free and overall survival was 4.1 months (95% CI, 2.2-5.4) and 10.4 months (95% CI, 8.1-14), respectively. The grade 3/4 hematological toxicities were neutropenia (36.7%), thrombocytopenia (3.3%), anemia (13.3%), and febrile neutropenia (6.6%). There were no grade 4 nonhematological toxicities. Frequent grade 3 nonhematological toxicities included diarrhea (10%), anorexia (6.6%), and hyponatremia (6.6%). CONCLUSIONS: This phase II study showed a high objective response rate and long survival. Irinotecan monotherapy schedule used was well tolerated, and could be an active treatment option for these patients.

Phase 1b safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer.

OBJECTIVE: Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha, over-expressed in epithelial ovarian cancer (EOC) but largely absent in normal tissue. Previously, carboplatin plus pegylated liposomal doxorubicin showed superior progression-free survival and an improved therapeutic index compared with carboplatin/paclitaxel in relapsed platinum-sensitive EOC. This study assessed safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive recurrent EOC. METHODS: This multicenter, single-arm study enrolled patients with platinum-sensitive EOC in first or second relapse for treatment with weekly farletuzumab 2.5mg/kg plus carboplatin AUC5-6 and pegylated liposomal doxorubicin 30mg/m(2) every 4weeks for 6cycles. Subsequently, maintenance with single-agent farletuzumab 2.5mg/kg once weekly or farletuzumab 7.5mg/kg once every three weeks continued until progression. The primary objective was to assess the safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin. RESULTS: Fifteen patients received a median of 12.0cycles (range, 3-26) of farletuzumab as combination therapy or maintenance, for a median of 45.0weeks (range 9-95). Farletuzumab/carboplatin/pegylated liposomal doxorubicin was generally well tolerated, with no farletuzumab-related grades 3-4 adverse events. The most commonly reported adverse events were associated with combination chemotherapy: fatigue (73.3%), nausea (46.7%), and neutropenia (40%). Ten patients had grade ≥3 adverse events, most frequently neutropenia and fatigue. No cardiac toxicity was seen. Best overall responses (RECIST) were a complete response for one patient, partial responses for 10 patients, and stable disease for four patients. CONCLUSIONS: Farletuzumab plus carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive EOC demonstrated a safety profile consistent with that of carboplatin plus pegylated liposomal doxorubicin.

Minimally invasive secondary cytoreduction plus HIPEC versus open surgery plus HIPEC in isolated relapse from ovarian cancer: a retrospective cohort study on perioperative outcomes.

STUDY OBJECTIVE: To compare the perioperative outcomes of minimally invasive secondary cytoreduction surgery (SCS) plus hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) versus open surgery plus HIPEC in a group of platinum-sensitive patients with advanced epithelial ovarian cancer (AEOC) with isolated relapse. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy. PATIENTS: We selected 22 patients with a peritoneal cancer index value of 2. The laparoscopic group consisted of 11 patients who underwent laparoscopic and/or robotic complete cytoreduction plus HIPEC, whereas the laparotomic group consisted of 11 patients who underwent complete laparotomic cytoreduction plus HIPEC. INTERVENTIONS: The minimally invasive surgery (MIS) group were platinum-sensitive single recurrent ovarian cancer patients who underwent either laparoscopic or robotic complete secondary cytoreduction plus HIPEC, whereas the open group were women with similar clinical characteristics who underwent complete secondary cytoreduction plus HIPEC by laparotomy. MEASUREMENTS AND MAIN RESULTS: The median operative time, calculated from the skin incision to the end of SCS (i.e., excluding HIPEC phase) was 125 min (range 95-150 min) in the MIS group and 295 min (range 180-420) in the open group (p = .001), with a median estimated blood loss of 50 mL (range 50-100) and 500 mL (range 50-1300), respectively (p = .025). The median length of hospital stay was 4 days (range 3-17) in the MIS group and 8.5 days (range 4-30) in the open group (p = .002). No statistically significant differences were registered in terms of intra- and postoperative complications between the 2 groups. CONCLUSION: The minimally invasive approach for SCS plus HIPEC is safe and efficient in terms of toxicity and postoperative outcomes for single isolated relapse. HIPEC should not be considered a major contraindication to a minimally invasive approach.

Minimally invasive secondary cytoreduction plus HIPEC for recurrent ovarian cancer: a case series.

OBJECTIVE: To analyze the feasibility of laparoscopic/robotic secondary cytoreductive surgery and hyperthermic intraperitoneal intra-operative chemotherapy (SCS+HIPEC) in a retrospective series of isolated platinum sensitive recurrent ovarian cancer. METHODS: We retrospectively evaluated a consecutive series of ovarian cancer patients with isolated platinum sensitive relapse. Isolated relapse was defined as the presence of a single nodule, in a single anatomic site. In all cases the presence of isolated relapse was assessed at pre-operative FDG-PET/CT scan, and confirmed with staging laparoscopy performed immediately before SCS+HIPEC. RESULTS: 84 women with platinum sensitive relapse received SCS+HIPEC during a 4-year period. Among them, 10 cases (11.9%) showed isolated relapse and were treated with laparoscopic/robotic SCS+HIPEC. In all cases complete debulking was achieved. In HIPEC treatment, 9 women received cisplatin at 75 mg/m(2), and the remaining patient oxaliplatin 460 mg/m(2). In 7 patients SCS was performed through the laparoscopic route, and in 3 cases with a robotic approach. The median operative time from skin incision to the end of cytoreductive surgery was 122 min (95-140), estimated blood loss was 50 cm(3) (50-100), and the median length of hospital stay was 4 days (3-7). The interval from surgery to adjuvant chemotherapy was 21 days (19-32). No grade 3/4 surgical, metabolic, or hematologic complications occurred. In all cases post-operative FDG-PET/CT scan was negative, and after a median time of 10 months (6-37) from SCS+HIPEC no secondary recurrence was observed. CONCLUSIONS: Minimally invasive SCS+HIPEC can be safely performed in selected ovarian cancer patients with platinum sensitive isolated relapse.

Low-dose irinotecan as a second-line chemotherapy for recurrent small cell lung cancer.

OBJECTIVE: Irinotecan is a potent inhibitor of deoxyribonucleic acid topoisomerase 1 and the weekly schedule of 100-125 or 350 mg/m(2) administration on Day 1 every 3 weeks is recommended for recurrent small cell lung cancer. However, severe gastrointestinal toxic effects and myelosuppression are often observed in this dose setting. We conducted a retrospective study to evaluate the efficacy and safety of low-dose irinotecan monotherapy (60 mg/m(2) on Days 1, 8 and 15 every 4 weeks) as second-line chemotherapy for small cell lung cancer. METHODS: The medical charts of small cell lung cancer patients who had received second-line chemotherapy at the National Cancer Center Hospital East between April 2003 and June 2012 were reviewed. Consecutive 57 patients who were treated with low dose of irinotecan (60 mg/m(2) on Days 1, 8 and 15 every 4 weeks) were analyzed in this study. RESULTS: Median age was 70 years (range, 51-83). Fifty-two (91%) were male, 36 (63%) had an Eastern Cooperative Oncology Group performance status 0-1 and 26 (46%) were sensitive relapse. The median number of chemotherapy cycles was 2. The objective response rate was 32% (95% confidence interval: 20-45%).The median progression-free survival and the median overall survival were 2.9 months (95% confidence interval: 1.9-3.4 months) and 5.3 months (95% confidence interval: 3.6-7.6 months), respectively. The incidence of Grade 3/4 neutropenia, diarrhea and nausea/vomiting was 21, 4 and 5%, respectively. CONCLUSIONS: Low-dose irinotecan monotherapy for recurrent small cell lung cancer might be effective with favorable toxicity. Randomized trial of 60 mg/m(2) versus standard dose of irinotecan is warranted.

Reconsidering the Cutoff Value for Sensitive and Refractory Relapses in Extensive-Stage SCLC in the Era of Immunotherapy.

INTRODUCTION: Traditionally, relapsed SCLC has been classified as "sensitive" or "refractory" on the basis of cutoff values (60 or 90 d) for the duration between the last chemotherapy and disease progression. Nevertheless, these cutoff values are not derived from rigorous analytical methods, and their applicability to contemporary treatments remains uncertain. METHODS: We conducted a retrospective multicenter study on patients with extensive-stage SCLC who underwent second-line therapy after platinum-doublet chemotherapy with or without immune checkpoint inhibitor (ICI) resistance before (pre-ICI cohort) and after (post-ICI cohort) approval of combination immunotherapy. We selected the optimal platinum-free interval cutoff value with the lowest two-sided p value in the multivariable Cox regression model for second-line overall survival. The internal validity of the chosen cutoff value was assessed using twofold cross-validation. RESULTS: There were 235 and 98 patients in the pre-ICI and post-ICI cohorts, respectively. In the pre-ICI cohort, the optimal cutoff was 59 days (p = 0.0001); the hazard ratio calculated using twofold cross-validation was 1.31 (95% confidence interval: 0.95-1.82]). In the post-ICI cohort, although the 60- and 90-day cutoff values could predict prognosis (60 d; p = 0.002, 90 d; p = 0.005), the optimal cutoff value was 75 days (p = 0.0002), which resulted in a median second-line overall survival of 15.9 and 5.0 months for patients with sensitive and refractory relapse, respectively (hazard ratio = 2.77, 95% confidence interval: 1.56-4.93). CONCLUSIONS: We clarified the previously ambiguous cutoff values for classifying relapsed SCLC and revealed that the 75-day cutoff most accurately predicts subsequent prognosis than the traditional cutoffs in the post-ICI era.

A Survival Analysis of Patients with Recurrent Epithelial Ovarian Cancer Based on Relapse Type: A Multi-Institutional Retrospective Study in Armenia.

BACKGROUND: Annually, approximately 200 new ovarian cancer cases are diagnosed in Armenia, which is considered an upper-middle-income country. This study aimed to summarize the survival outcomes of patients with relapsed ovarian cancer in Armenia based on the type of recurrence, risk factors, and choice of systemic treatment. METHODS: This retrospective case-control study included 228 patients with relapsed ovarian cancer from three different institutions. RESULTS: The median age of the patients was 55. The median follow-up times from relapse and primary diagnosis were 21 and 48 months, respectively. The incidence of platinum-sensitive relapse was 81.6% (186), while platinum-resistant relapse was observed in only 18.4% (42) of patients. The median post-progression survival of the platinum-sensitive group compared to the platinum-resistant group was 54 vs. 25 months (p < 0.001), respectively, while the median survival after relapse was 25 vs. 13 months, respectively; three- and five-year post-progression survival rates in these groups were 31.2% vs. 23.8%, and 15.1% vs. 9.5%, respectively (p = 0.113). CONCLUSIONS: Overall, despite new therapeutic approaches, ovarian cancer continues to be one of the deadly malignant diseases affecting women, especially in developing countries with a lack of resources, where chemotherapy remains the primary available systemic treatment for the majority of patients. Low survival rates demonstrate the urgent need for more research focused on this group of patients with poor outcomes.

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer.

OBJECTIVE: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. METHODS: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. RESULTS: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2-6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4-46.4%), and the DCR was 65.2% (95% CI, 56.4-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. CONCLUSIONS: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

Re-challenge chemotherapy in patients with sensitive relapse small-cell lung cancer and interstitial lung disease.

BACKGROUND: Treatment modalities for small-cell lung cancer (SCLC) with pre-existing interstitial lung disease (ILD) are limited. Although re-challenge with first-line chemotherapy can be effective for sensitive relapse SCLC, its safety and efficacy are uncertain in cases with ILD. This study aimed to investigate both the efficacy and safety of re-challenge chemotherapy in patients with sensitive relapse SCLC with ILD. METHODS: Patients with sensitive relapse SCLC with ILD who received re-challenge chemotherapy were studied retrospectively. Sensitive relapse was defined as a treatment-free interval (TFI) of more than 60 days after first-line platinum-based treatment. The endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Re-challenge platinum and etoposide were administered in 11 patients, with the median re-challenge cycle of 3. The overall response rate was 55%. The median PFS and OS from the time of re-challenge treatment were 4 months (95% CI, 2.9-NA) and 9.2 months (95% CI, 8.0-NA), respectively. One patient developed acute exacerbation of ILD 173 days after the last course of re-challenge treatment. CONCLUSIONS: Re-challenge chemotherapy can be effective and considered in SCLC patients with pre-existing ILD.

Efficacy of Second-line Chemotherapy in Patients With Sensitive Relapsed Small-cell Lung Cancer.

BACKGROUND/AIM: To evaluate treatment efficacy of cisplatin, etoposide, and irinotecan combined therapy (PEI), platinum-rechallenge chemotherapy (Pt-Re) and amrubicin monotherapy (AMR) for patients with sensitive relapsed small cell lung cancer (SCLC). PATIENTS AND METHODS: We defined sensitive relapse as treatment-free interval (TFI) ≥90 days. We retrospectively collected patients' data from medical records between September 2002 and December 2016. Patients with sensitive relapsed SCLC who received second-line chemotherapy were separated into those treated with PEI, with Pt-Re, or with AMR. RESULTS: Seventy-one patients (16 PEI group, 27 Pt-Re group, and 28 AMR group) were assessable for efficacy. No significant differences in patient characteristics were found among the three groups. The median overall survival (MST) was 29.3 months in the PEI group, 24.6 months in the Pt-Re group, and 20.6 months in the AMR group (p=0.042). CONCLUSION: A significant difference was observed in the overall survival of patients treated with PEI, Pt-Re and AMR and the MST of PEI was the longest.

Trabectedin in Ovarian Cancer: is it now a Standard of Care?

In patients with recurrent ovarian cancer, the choice of second-line therapy is complex. Several factors have to be considered, such as platinum-free interval (PFI), residual toxicity from the previous treatments, BRCA1/2 gene mutation status. Trebectedin is a minor groove DNA binder derived from a marine organism that has shown efficacy in different settings in ovarian cancer therapy. It has been approved in the treatment of partially platinum sensitive (PPS) (PFI between 6 and 12 months) relapsed ovarian cancer according to the statistically significant progression-free survival (7.3 versus 5.8 months) and overall survival (22.2 versus 18.9 months) benefit compared with single-agent pegylated liposomal doxorubicin (PLD) in the OVA 301 phase III trial. This drug has been shown to prolong the time to first subsequent treatment and improve the efficacy of further platinum-based chemotherapy. The role of trabectedin/PLD followed by platinum combination compared with the reverse sequence in PPS is actually in evaluation in the INOVATYON phase III study, which will clarify the best sequence to be adopted in this setting. Trabectedin has been shown to be active in patient carriers of BRCA mutations, probably for its mechanism of action directly affecting DNA and it is actually tested as a single agent in some phase III trials in BRCA mutated and BRCAness ovarian cancer patients. Trabectedin is also active on the immune system. There is, therefore, the rational for new trials of a combination with immune checkpoint inhibitors.

The effect of post-progression survival on overall survival among patients with sensitive relapse of small cell lung cancer.

Recent studies have suggested that, among patients with advanced lung cancer, subsequent treatment after failure of first-line or second-line chemotherapy has a greater effect on overall survival (OS) than tumor shrinkage or progression-free survival (PFS). However, no studies have examined this issue among patients with sensitive relapse of small cell lung cancer (SCLC). We retrospectively evaluate 77 patients with sensitive relapse of SCLC who received second-line chemotherapy after first-line platinum doublet chemotherapy between January 1999 and November 2013. The analyses included patient characteristics, treatment parameters, tumor shrinkage, PFS, post-progression survival (PPS), and OS. Spearman rank correlation analysis and linear regression analysis revealed that PPS was strongly correlated with OS (r = 0.91, p < 0.01, R2 = 0.96), PFS was moderately correlated with OS (r = 0.58, p < 0.01, R2 = 0.28), and tumor shrinkage was weakly correlated with OS (r = 0.34, p < 0.01, R2 = 0.12). A multivariate Cox proportional hazards model with a stepwise regression procedure revealed that PPS was significantly associated with age at the start of second-line chemotherapy, best response to second-line and third-line chemotherapy, and the number of regimens after progression beyond second-line chemotherapy (p < 0.05). These findings suggest that PPS has a stronger effect than PFS on OS among patients with sensitive relapse of SCLC. Thus, response to second-line chemotherapy and subsequent treatment for disease progression after second-line chemotherapy may be important factors that influence OS.

Rechallenge treatment with a platinum-based regimen in patients with sensitive relapsed small-cell lung cancer.

Among patients with relapsed small-cell lung cancer (SCLC), those who relapse > 90 days after first-line chemotherapy are classified sensitive relapse. Rechallenge with a first-line platinum-based regimen has been used in sensitive relapsed SCLC patients, but its importance is not known. We evaluated the outcome of rechallenge with platinum-based chemotherapy for sensitive relapse patients. We reviewed consecutive patients with sensitive relapsed SCLC who received second-line chemotherapy between January 1999 and December 2016. We evaluated the treatment outcomes of platinum-based rechallenge and non-rechallenge regimens for second-line chemotherapy in sensitive relapse patients. Of 245 patients, 81 sensitive relapse patients received second-line chemotherapy. Sixty-seven patients (82.7%) were treated with rechallenging platinum-based regimens ("rechallenge group") and 14 patients (17.3%) were treated with other regimens ("non-rechallenge group") as second-line chemotherapy. Median progression-free survival (PFS) was 5.1 months in the rechallenge group and 3.5 months in the non-rechallenge group, and median survival time was 10.8 and 8.2 months, respectively. There were no significant differences in PFS or overall survival (OS) between the two groups. Sub-analyses of patients who received chemotherapy alone as first-line treatment showed that the rechallenge group had longer PFS than that of the non-rechallenge group (median 5.4 vs. 3.6 months, p = 0.0038), and the rechallenge group had a tendency to have longer OS than non-rechallenge group. These data suggest that rechallenge treatment with a platinum-based regimen could be second-line chemotherapy in patients with sensitive relapsed SCLC, especially those treated with chemotherapy alone as first-line therapy.

Rechallenge with First-Line Platinum Chemotherapy for Sensitive-Relapsed Small-Cell Lung Cancer.

BACKGROUND: Sensitive-relapsed small-cell lung cancer (SCLC) is thought to be sensitive to chemotherapy; therefore, second-line chemotherapy is recommended. Although platinum rechallenge is performed in the second-line chemotherapy for sensitive-relapsed SCLC, it remains unclear whether such a strategy is effective. METHODS: We retrospectively analyzed the outcome of rechallenge chemotherapy for sensitive-relapsed SCLC. The endpoints of this study were progression-free survival from the time of relapse (PFS-Re) and overall survival from the time of relapse (OS-Re). We also compared the toxicity profile of rechallenge chemotherapy to that of first-line chemotherapy. RESULTS: Of the 133 SCLC patients who received first-line treatment, 20 patients satisfied the definition of sensitive relapse and received rechallenge chemotherapy. Combined carboplatin and etoposide was the most commonly used rechallenge regimen, and 17 (85%) received it at a reduced dose due to hematological toxicity during the first-line treatment. Median PFS-Re and OS-Re were 4.5 months (95% CI: 3.5-5.4) and 10.5 months (95% CI: 7.9-13.0), respectively. There was no association between dose adjustment and survival. The frequency of hematologic toxicity tended to be lower with rechallenge than first-line treatment. The incidence of grade 3 febrile neutropenia decreased from 40% in first-line treatment to 15% in rechallenge. CONCLUSION: Platinum rechallenge could be a useful second-line option for sensitive-relapsed SCLC, having favorable efficacy and safety. Dose adjustment at rechallenge based on the toxicity profile during the first-line chemotherapy could reduce toxicity without weakening efficacy.

Traitement des rechutes tardives du cancer de l'ovaire.

TREATMENT FOR PLATINUM SENSITIVE RELAPSES OF OVARIAN CANCER: Despite large improvements in treatment efficacy, the cure rate of ovarian cancer has not radically changed. Relapses both remain frequent and are still synonymous with chronic disease. Most of them are platinum-sensitive, and can be successfully treated with successive lines of chemotherapy. Surgery may have a role to play but its real impact, population selection criteria, and adequate timing still have to be established. Regarding medical treatments, the availability of new targeted therapeutics, such as bevacizumab and olaparib, complicates decision making. Moreover, allergic drug reactions to platins worsen treatment management. In practice, treatment decision making integrates patient profiles and wishes, types and numbers of previous medical treatments along with BRCA status.

Validation of standard definition of sensitive versus refractory relapsed small cell lung cancer: a pooled analysis of topotecan second-line trials.

BACKGROUND: Relapsed small cell lung cancer (SCLC) is classified into sensitive or resistant according to treatment-free interval (TFI) longer or shorter than 60 (criteria 1) or 90 (criteria 2) days. However, these criteria are based on small old studies and are inconsistent among different studies. The present study aimed at validating these criteria and assessing additional clinical parameters predictive of response rate (RR) and overall survival (OS). PATIENTS AND METHODS: A database of six GlaxoSmithKline-sponsored trials of intravenous topotecan-based second-line chemotherapy was analysed. Validation of sensitive/resistant definition was performed on the entire dataset (631 patients), while study of additional parameters and development of prognostic model was conducted dividing the database into derivation and validation sets. RESULTS: The association between criterion 1 or 2 and RR was confirmed. Changing TFI cut-off or adding response to first-line did not improve accuracy. In addition to TFI (P=0.007), only presence of liver metastasis (P=0.046) was found to affect the probability of objective response. TFI, age, liver metastases, performance status (PS), albumin, haemoglobin and sodium levels were identified as independent prognostic factors for OS. A prognostic model, based on these variables, was able to separate relapsed SCLC into low versus high risk categories (median OS 41.4 versus 20.0 weeks). CONCLUSIONS: This study confirms the value of standard criteria for relapsed SCLC outcome prediction. Patients with TFI<60 days are refractory to second-line chemotherapy and have poor OS. Patients with liver metastasis and/or PS2 and/or low albumin, regardless of TFI, have similarly poor outcome.

Relapsed small cell lung cancer: treatment options and latest developments.

According to recent analyses, there was a modest yet significant improvement in median survival time and 5-year survival rate of limited stage small cell lung cancer (SCLC) in North America, Europe, Japan and other countries over the last 30 years. The median survival time of limited stage SCLC is 15-20 months and 5-year survival rate is 15% or less. In terms of extensive stage SCLC, a median survival time of 9.4-12.8 months and 2-year survival of 5.2-19.5% are still disappointing. Despite being highly sensitive to first-line chemotherapy and radiotherapy treatments, most patients with SCLC experience relapse within 2 years and die from systemic metastasis. While several clinical trials of cytotoxic chemotherapies and molecular targeting agents have been investigated in the treatment of relapsed SCLC, none showed a significant clinical activity to be able to exceed topotecan as second-line chemotherapy. There are problematic issues to address for relapsed SCLC, such as standardizing the treatment for third-line chemotherapy. Topotecan alone was the first approved therapy for second-line treatment for relapsed SCLC. Amrubicin is a promising drug and a variety of trials evaluating its efficacy have been carried out. Amrubicin has shown superiority to topotecan in a Japanese population, but was not superior in a study of western patients. There are some controversial issues for relapsed SCLC, such as treatment for older patients, third-line chemotherapy and efficacy of molecular targeting therapy. This article reviews current standard treatment, recent clinical trials and other topics on relapsed SCLC.

Successful Retreatment With ADOC Chemotherapy in Relapsed Thymic Carcinoma: Experiences in Two Cases.

The optimal second-line chemotherapeutic regimen for thymic carcinoma remains uncertain and predictive factors for the response have not been identified. We encountered two cases of relapsed thymic carcinoma with recurrence 1.5 and 8 years after initial response to cisplatin/doxorubicin/vincristine/cyclophosphamide (ADOC) chemotherapy. Both cases were successfully retreated with ADOC. Our observations suggest that relapsed thymic carcinoma occurring a long treatment-free time from the initial response may be sensitive to the previous chemotherapy. We described two cases of relapsed thymic carcinoma successfully retreated with ADOC chemotherapy. Both patients had partial response to initial ADOC and long disease free times.

Review of the management of relapsed small-cell lung cancer with amrubicin hydrochloride.

Lung cancer is the leading cause of cancer death, and approximately 15% of all lung cancer patients have small-cell lung cancer (SCLC). Although second-line chemotherapy can produce tumor regression, the prognosis is poor. Amrubicin hydrochloride (AMR) is a synthetic anthracycline anticancer agent and a potent topoisomerase II inhibitor. Here, we discuss the features of SCLC, the chemistry, pharmacokinetics, and pharmacodynamics of AMR, the results of in vitro and in vivo studies, and the efficacy and safety of AMR monotherapy and combination therapy in clinical trials. With its predictable and manageable toxicities, AMR is one of the most attractive agents for the treatment of chemotherapy-sensitive and -refractory relapsed SCLC. Numerous studies are ongoing to define the applicability of AMR therapy for patients with SCLC. These clinical trials, including phase III studies, will clarify the status of AMR in the treatment of SCLC.