Efficacy Of Second-line Chemotherapy Research Articles

Second-line chemotherapy in patients with primary unknown cancer

There are few existing reports on the efficacy of second-line chemotherapy in patients with cancer of unknown primary site (CUP). The aim of this study was to identify characteristics of CUP patients linked to a positive response to chemotherapy. We retrospectively studied the clinical outcomes of second-line chemotherapy in patients with CUP who had previously been treated with platinum-based first-line chemotherapy. A total of 27 patients received second-line chemotherapy. Of these patients, 5 (19%) showed an objective response to second-line chemotherapy; 4 of these patients had shown a favorable response to first-line chemotherapy and had a chemotherapy-free interval (CFI) of more than 4.5months. Among the 8 patients in whom the CFI was more than 4.5months, 4 (50%) showed an objective response to platinum-based second-line chemotherapy, whereas among the 16 patients with a CFI of less than 4.5months, only 1 (6%) showed a response to any chemotherapeutic regimen. The response to second-line chemotherapy in CUP patients who had received platinum-based first-line treatment seemed to be associated with the response to first-line chemotherapy and the CFI. Although it remains unclear whether second-line chemotherapy might contribute to a survival benefit in patients with CUP, patients who show a favorable response to first-line chemotherapy and also a relatively prolonged CFI appear to be likely to benefit from second-line chemotherapy.

Second-line therapy for small-cell lung cancer

Small-cell lung cancer (SCLC) recurs in the majority of patients, even though most patients respond to first-line therapy. Therefore second-line therapy is considered in almost all patients with SCLC in the course of disease. Efficacy of second-line chemotherapy is much lower than that of first-line treatment, but it can provide significant palliation and prolongation of survival for many patients. Patients receiving second-line therapy are divided into relapsed and refractory patients. Relapsed disease is defined as relapse or progression at least 3 months after the end of first-line therapy. All other situations, including a treatment-free interval <3 months or no response to first-line therapy, are termed refractory disease. The benefit from second-line chemotherapy is highest in patients with relapsed disease. Topotecan monotherapy improves survival and quality of life, as well as cancer-related symptoms in the second-line setting. Alternatively, doxorubicin-based combination therapy can be administered with a similar outcome but a slightly lower rate of symptom control. In refractory patients no standard therapy exists. Amrubicin, a novel anthracyline, showed promising activity in refractory and relapsed patients. Phase III trials are ongoing. Other agents with activity include irinotecan, paclitaxel, docetaxel, gemcitabine, bendamustine and vinorelbine.

Feasibility and efficacy of second-line chemotherapy at recurrence for pediatric low-grade gliomas: A comparative population-based study

2069 Background: Chemotherapy is widely accepted as the first-line therapy for pediatric low-grade gliomas (PLGG). Treatment modalities for further progression are controversial. Radiation therapy is still widely used, but the role for repeated chemotherapy remains unclear. The aim of the study was to determine treatment outcome for PLGG treated by chemotherapy at recurrence. Methods: The study group consisted of patients who received chemotherapy due to progression after initial chemotherapy protocol. These were compared to patients treated with chemotherapy at diagnosis, patients who received chemotherapy at third progression and to patients who received radiotherapy at recurrence. Results: From 1990–2007, 80 patients received chemotherapy as first-line treatment for PLGG. 36 received chemotherapy as second-line and 11 at further recurrence. 31 patients were treated with radiation at recurrence. There was no gender preference. Median follow-up time was 6.85 yrs. Histology revealed grade 1 astrocytoma in 73%. The most common location was optic pathway with 49%, followed by brainstem and suprasellar (14 %) and thalamic and spinal location (11 %). The most common initial protocol was vincristine and carboplatin (80%). The most common protocol at relapse was vinblastine (87%). Five-year progression-free survival (PFS) for first-line chemotherapy was 49% ± 6 compared to 41 ± 9% with second-line chemotherapy (p=0.2). For further chemotherapy PFS was comparable but so far with shorter follow-up. Five years PFS for the second-line chemotherapy and radiotherapy at recurrence group were 41 ± 9% and 78 ± 5 % respectively (p=0.003). Only 4 patients died, out of whom only 2 due to tumor progression. Conclusions: This is the first study to address the role of chemotherapy for recurrent PLGG. In contrast to other tumours chemotherapy at diagnosis as well as at first recurrence is associated with similar outcome. Nevertheless in this study radiotherapy was superior to chemotherapy. Prospective studies to assess toxicity and long-term outcome are needed. No significant financial relationships to disclose.

The Role of Second-Line Chemotherapy After Gemcitabine Failure In Patients With Advanced Pancreatic Cancer

Systemic chemotherapy with single-agent gemcitabine or a gemcitabine-based regimen still remains a standard of care for the treatment of patients with locally advanced and metastatic pancreatic cancer. To date, no standard treatment approach for patients that show progressive disease during gemcitabine therapy is defined. Several clinical trials have evaluated the safety and efficacy of second-line chemotherapy after gemcitabine failure in this patient population. Based on the currently available data, there is increasing evidence that selected patients may derive clinical benefit from salvage chemotherapy, also with regard to survival. However, results from large randomized Phase III trials are still lacking and therefore no evidence-based treatment recommendation can be given for patients with advanced pancreatic cancer after failure of first-line gemcitabine.

The efficacy of second line chemotherapy (CHT) in platinum-sensitive advanced/metastatic small cell lung cancer (SCLC) patients: Results of an ongoing Italian multicenter survey

18090 Background: Despite CHT and radiotherapy for SCLC, most patients (pts) die within 2 years. Response rates for second-line CHT are low, with a median survival of 5 months in platinum-refractory pts. Re-challenge with platinum salts or salvage regimens is a standard option for pts with platinum-sensitive disease with a median overall survival (OS) of 6.5–8 months (Chua et al., Cancer Treat Rev. 2004). The purpose of this study was to explore the benefits of different second line regimens in this platiunum sensitive population. Methods: Clinical records of 73 platinum sensitive SCLC pts (first line relapse free survival &gt; 6 months) were reviewed from 13 medical oncology departments in Italy from January 1993 to December 2006. Pt. characteristics: 59 males, 14 females, median age 64 years (range 27–93), median ECOG performance status (PS): 1, limited/extended disease: 33/40 pts. Pts received salvage chemotherapy which consisted of monotherapy in 37% and platinum-containing doublets in 55%. Doublets without platinum salts were administered in the remaining 8%. Results: Of 67 evaluable pt, second line CHT produced partial responses (PR) in 58 (79%) and stable disease (SD) in 9 pts (12%) by RECIST criteria. Overall tumor growth control (PR+SD) was 91%. Despite these encouraging results, the median TTP was 3 months and OS for all evaluable pts was 6.5 months. Survival at 1 year was 11%. Multivariate analysis revealed that the most important prognostic factor for response was age ( p&lt;0.04) and there was no statistically significant difference between platinum-based regimens and monotherapy. Multivariate analysis showed no impact on survival by prior response to first line treatment, female sex or smoking status. Conclusions: Within the limits of a retrospective study, despite the high rate of responses obtainable in this setting, TTP and OS do not appear significantly improved by salvage regimens. Second line CHT has marginal activity and should be considered only in younger pts with a good PS. On the basis of these results, re-treatment with platinum salts could be avoided in these pts. No significant financial relationships to disclose.

Prognostic factors for response and survival of second-line chemotherapy in patients with relapsed small cell lung cancer (SCLC)

18023 Background: Despite high response rates to initial chemotherapy, the majority of patients with SCLC experience tumor progression. Previous studies showed that both the response to initial chemotherapy and the response duration are important for predicting the efficacy of second-line chemotherapy. Therefore, relapsed SCLC is commonly classified into two groups: sensitive relapse (respond to initial chemotherapy and relapse more than 3 months after the completion of initial chemotherapy) and refractory relapse (not respond to initial chemotherapy or respond but relapse within 3 months). However, prognostic factors of the second-line chemotherapy have not been fully understood. Methods: From July 1992 to December 2003, four hundred and seventy-four patients with SCLC received chemotherapy as initial treatment, subsequently 229 patients received second-line chemotherapy (144 sensitive relapse and 85 refractory relapse) in our hospital. We analyzed the association of patients’ clinical factors with response and survival of second-line chemotherapy in sensitive relapsed patients and refractory relapsed patients, separately. For sensitive relapsed patients, analyzed clinical factors were as follows: age (&lt;70/=70), gender (M/F), response to initial chemotherapy (CR/PR), PS at relapse (&lt;2/=2) and the extent of disease at relapse (LD/ED). For refractory relapsed patients, analyzed clinical factors were as follows: age (&lt;70/=70), gender (M/F), response to initial chemotherapy (responder/non-responder), PS at relapse (&lt;2/=2) and the extent of disease at relapse (LD/ED). Results: Response to second-line chemotherapy was significantly correlated with PS in sensitive relapsed patients, however, no significant factor was detected in refractory relapsed patients. For survival, PS was the only significant prognostic factor in both sensitive and refractory relapsed patients. The median survival time was 328 days (PS&lt;2) and 128 days (PS=2) in sensitive relapsed patients (p&lt;0.0001), while 195 days (PS&lt;2) and 113 days (PS=2) in refractory relapsed patients (p=0.0001), respectively. Conclusions: PS was the only significant prognostic factor for survival both in sensitive and refractory relapsed SCLC. No significant financial relationships to disclose.

Doublet regimen of cisplatin plus docetaxel for second-line chemotherapy after prior therapy with cisplatin plus irinotecan for non-small cell lung cancer: a phase II study

To evaluate the safety and efficacy of second-line chemotherapy with docetaxel and cisplatin for non-small cell lung cancer (NSCLC), we performed a phase II study. The subjects were 25 patients with NSCLC, 75 years or younger, without organ dysfunction (performance status [PS], 0 to 2) in whom treatment with cisplatin and irinotecan had been ineffective or had been followed by recurrence or relapse. Four weeks or more after the end of the previous therapy, 60 mg/m2 of cisplatin and 60 mg/m2 of docetaxel were administered at intervals of 3 weeks. Observed toxicities of grade 3 or 4 included anemia (24% of patients), leukocytopenia (48%), neutropenia (76%), thrombocytopenia (4%), hepatic dysfunction (8%), and electrolyte abnormalities (4%). However, no severe nonhematologic adverse reactions occurred. The overall response rate was 32% (95% confidence interval, 13.7-50.3). The median time to disease progression was 98 days, and the median survival time was 257 days. Our results suggest that cisplatin and docetaxel can be used as second-line chemotherapy against NSCLC. But further, comparative, study of this combination should be performed in patients with good PS and organ function who have responded to prior platinum-based chemotherapy.