Survival and Toxicity Following Chemoradiation for Carcinoma of the Cervix - Impact of Multiple-phase Treatment and Shielding.

AIM: We report on outcomes and significant grade 3-4 late toxicities between January 1999 and October 2006 following introduction of multi-phase treatment and effect of shielding in treatment of cervical cancer with concurrent chemoradiation. PATIENTS AND METHODS: Radiotherapy dose by phase, recurrence, survival and toxicity data was collated by a retrospective review of clinical notes. Shielding information was retrieved from original planning films. RESULTS: 3-year survival for stages I, II and III disease were 89%,76% and 51% respectively. Local pelvic failure was 9%. Overall significant late toxicity (SLT) rate was 13%, with lower rates for post-operative treatment than primary chemoradiation (4% vs. 16%). SLT with single phase treatment was 29% versus 12% following multiphase EBRT and 16% when <2 areas were shielded versus 6% with ≥3 shielded areas (p=0.01). CONCLUSION: Shielding and multi-phase treatment not only reduce dose to organs at-risk but can also reduce late toxicity without compromising local control or survival.

Chemotherapy for Uterine Carcinosarcoma with Carboplatin, Ifosfamide and Mesna.

BACKGROUND/AIM: Uterine carcinosarcomas (UCSs) are highly aggressive, rare, biphasic tumors composed of epithelial and mesenchymal elements. Surgery remains the mainstay of treatment in early-stage disease. Adjuvant pelvic radiotherapy improves locoregional control without proven overall survival (OS) benefit. Although adjuvant ifosfamide-based combination chemotherapy with cisplatin or paclitaxel has shown superiority to radiotherapy or single-agent chemotherapy in randomized controlled trials, there is no consensus on a standard regimen due to toxicities. The aim of this retrospective study was to assess the efficacy and toxicity of a novel combination chemotherapy using carboplatin, ifosfamide and mesna (CIM) and compare with other regimens for patients with UCSs in both the adjuvant and palliative setting. PATIENTS AND METHODS: Between 1997 and 2010, 60 patients with UCS, 70% of whom with international federation of gynecology and obstetrics (FIGO) stage III/IV disease, were treated with adjuvant or palliative chemotherapy. Two groups were identified: Group1 (n=22) included patients receiving CIM chemotherapy; and group 2 (n=38) receiving other regimens (carboplatin/paclitaxel/cisplatin/doxorubicin/epirubicin). RESULTS: After a median follow-up of 60 months, disease in seven patients in group 1 (CIM) and 20 patients in group 2 had progressed/relapsed. Out of these, six patients in group 1 and 13 patients in group 2 had died. The progression-free survival (PFS) and OS for patients treated with adjuvant or palliative CIM was 35 months [95% confidence interval (CI) =0.26-0.43] and 47 months (95% CI=0.38-0.56; log-rank, p=0.001) respectively, whereas for group 2 patients treated with other regimens, PFS was 27.48 months (95% CI=0.20-0.33) and OS was 30 months (95% CI=0.21-0.38; log-rank, p=0.001). While none of the patients in group 1 experienced neurotoxicity or other grade 3 or 4 toxicities, 3/38 patients in group 2 experienced grade 3 neutropenia, 4/38 had peripheral sensory neuropathy, 6/38 patients had treatment deferred due to toxicities or allergic reaction to paclitaxel. CONCLUSION: In the phase III randomized controlled trial combination of ifosfamide and taxanes has shown PFS and OS benefit when compared to single-agent ifosfamide at the expense of significant toxicities. Results from our study show that the combination of CIM is an effective and safe alternative regimen for patients with advanced UCSs. In addition to improved OS and PFS, the main advantage of this regimen over taxane-based regimens includes minimal neuropathy, less use of steroids, and low risk of allergic reaction. CIM should be considered in future prospective studies looking at the treatment of UCS.

Chemotherapy for advanced endometrial cancer with carboplatin and epirubicin.

UNLABELLED: Endometrial cancer is the most common gynecological cancer in the Western world. In early-stage disease, surgery remains the mainstay of treatment. Adjuvant pelvic radiotherapy reduces the risk of pelvic recurrence, however, without improvement in overall survival. The aim of the present study was to assess the efficacy and toxicity of carboplatin and epirubicin combination chemotherapy for patients with advanced and high-risk endometrial cancer. PATIENTS AND METHODS: Between 1999 and 2007, 43 patients with endometrial cancer were treated with carboplatin and epirubicin. Two groups were identified: Group 1 (n=34) included patients with stage III endometrial cancer receiving adjuvant chemotherapy; and group 2 included those with metastatic endometrial cancer (n=9). RESULTS: After a median follow-up of 37 months, disease in 19 patients had progressed/relapsed (12 patients from group 1; 7 from group 2) and 23 patients had died (15 from group 1; 8 from group 2). The median time-to-progression was 62 months and median overall survival was 64 months. The median survival for patients in group 1 was 69 months and for those in group 2 was 22 months. Ten patients (27.9%) experienced grade 3 or 4 toxicities. There were no cases of treatment-related cardiac failure or neuropathy. CONCLUSION: Cisplatin, carboplatin, anthracyclines and taxanes are the most active agents in endometrial cancer. Combination chemotherapy leads to better progression-free survival and overall survival, however, this is at the expense of increased toxicity. RESULTS from our study show that the combination of carboplatin and epirubicin is an effective alternative regimen for patients with advanced endometrial cancer. In addition, treatment-related toxicity is minimal when compared to anthracyclines and platinum agents. There is a particular advantage of this regimen over taxane-based regimens, including minimal neuropathy, less use of steroids and low risk of allergic reaction and alopecia.

Unilateral onycholysis in a patient taking erlotinib (Tarceva).

Targeting epidermal growth factor receptor (EGFR)-mediated signalling pathways has become routine practice in the treatment of lung cancer. Erlotinib is an oral EGFR tyrosine kinase inhibitor, licensed for maintenance monotherapy treatment in patients with locally advanced or metastatic non-small cell lung cancer after first-line chemotherapy. The authors present the case of a 51-year-old patient who had an excellent response to erlotinib, but developed unilateral onycholysis as an unusual side effect. The authors discuss erlotinib-induced skin and nail changes and have provided a brief literature review on the available evidence for their management.

Managing a locally advanced malignant thymoma complicated by nephrotic syndrome: a case report.

INTRODUCTION: The management of locally advanced inoperable malignant thymoma is difficult as there are no large randomized clinical trial data to guide treatment. However various case series have shown that malignant thymoma is often a chemosensitive disease. Cisplatin-based chemotherapy has been the gold-standard in the management of these patients. However when thymic cancers are complicated by paraneoplastic syndromes that damage kidney and neurological function, cisplatin use is often contraindicated. CASE PRESENTATION: We report a case of a 37 year old man with locally advanced malignant thymoma complicated by significant nephrotic syndrome and renal impairment. He responded to a novel combination of carboplatin, epirubicin and cyclophosphamide chemotherapy used as first line therapy. CONCLUSION: The treatment with chemotherapy of locally advanced malignant thymoma complicated by nephrotic syndrome and renal impairment is difficult due to the increase of toxicity. In this case, a novel chemotherapy combination with lesser toxicity was used successfully. In addition this chemotherapy combination did not impede the later use of conventional cisplatin-based chemotherapy. Therefore we suggest a course of carboplatin-based chemotherapy for locally advanced malignant thymoma in patients who are unsuitable for cisplatin.