Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report.

Leptomeningeal carcinomatosis represents a rare manifestation of metastatic breast cancer (MBC). We herewith report on a patient suffering from HER2 overexpressing MBC who received intrathecal methotrexate and trastuzumab for meningeal carcinomatosis. A 48-year-old woman was diagnosed with breast cancer in December 2002. Following surgery, six cycles of adjuvant FE100C plus irradiation and, subsequently for 1 year, trastuzumab were given. As a result of disseminated metastatic spread in October 2005, the patient received whole-brain radiotherapy for symptomatic central nervous system involvement, and was put on several trastuzumab-based combination regimens (capecitabine, vinorelbine, paclitaxel). In June 2006, the patient developed clinical signs of terminal cone involvement with overflow incontinence and paraparesis of the legs. Immediate radiation led to partial relief from clinical symptoms. Subsequently, the patient was put on the tyrosine kinase inhibitor lapatinib and capecitabine (August to October 2007), but on November 6th the patient suffered again from overflow incontinence and weakness of the legs. Failing to respond to lapatinib, the patient received gemcitabine/cisplatin and, additionally, was recommenced on intravenous trastuzumab. Owing to progressive leptomeningeal disease, the patient received repeated doses of intrathecal methotrexate and trastuzumab. Within 2 weeks and four intrathecal treatments, cerebrospinal fluid cytology showed the absence of tumor cells. Moreover, a striking clinical improvement with resolution of the paraparesis of the legs and overflow incontinence was observed. This case report gives details regarding the clinical course of a breast cancer patient who received intrathecal trastuzumab and methotrexate via lumbar puncture for meningeal carcinomatosis of HER2-overexpressing MBC.

Effective second-line treatment with cetuximab and bevacizumab in a patient with hepatic metastases of colorectal cancer and hyperbilirubinemia.

BACKGROUND: Irinotecan-based second-line chemotherapy of metastatic colorectal cancer (CRC) is effective, it might, however, be contraindicated in cases of severe liver dysfunction due to advanced liver metastases. CASE REPORT: A 57-year-old woman with diffuse CRC liver metastases showed progressive disease on first-line treatment with capecitabine and oxaliplatin (XELOX). Chronic cholestasis and hyperbilirubinemia caused by advanced liver involvement prohibited second-line treatment with irinotecan-based chemotherapy. We initiated combined antibody treatment with cetuximab and bevacizumab. RESULTS: Clinical performance status as well as laboratory parameters improved rapidly. Staging investigations after 8 weeks revealed a partial remission. Since bilirubin levels had returned to the upper limit of normal, therapy could be changed to standard irinotecan, 5-fluorouracil, folinic acid, and bevacizumab. CONCLUSION: Combined treatment with cetuximab and bevacizumab may be considered as an effective treatment option in patients who cannot be treated with standard chemotherapy regimens due to impaired liver metabolism of cytotoxic substances.

Importance of CEA and CA 15-3 during disease progression in metastatic breast cancer patients.

UNLABELLED: The aim of this study analysis was to determine the correlation between elevation of CEA and/or CA 15-3 and disease progression of metastatic breast cancer. MATERIALS AND METHODS: We investigated 119 breast cancer patients who had metachronous metastases. We evaluated levels of CEA and CA 15-3 at the time of first recurrence and at every further disease progression (PD). RESULTS: Increasing value levels of CEA as well as CA 15-3 were found in correlation to the number of PD with a continuously increasing sensitivity in the detection of metastatic disease for each marker alone and especially in combination. At the first time of distant metastasis, CEA and CA 15-3 were above the 95th percentile of healthy individuals in 53.5% and 71.8%, respectively. During disease progression the sensitivities were: 1st PD for CEA/ CA 15-3 54.1%/ 70.6%, 2nd PD 63.5%/ 81.2% and 3rd PD 68.6%/ 90%. CONCLUSION: There is a correlation between elevation of CEA and/or CA 15-3 and disease progression, in breast cancer patients.

Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer.

OBJECTIVE: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem) failure has been defined for patients with advanced pancreatic cancer (PC). Oral capecitabine (Cap) has shown promising activity in first-line chemotherapy trials in PC patients. METHODS: Within a prospective single-center study, Cap was offered to patients who had already received at least 1 previous treatment regimen containing full-dose Gem (as a single agent, as part of a combination chemotherapy regimen or sequentially within a chemoradiotherapy protocol). Cap was administered orally at a dose of 1,250 mg/m(2) twice daily for 14 days followed by 7 days of rest. Study endpoints were objective tumor response rate by imaging criteria (according to RECIST), carbohydrate antigen 19-9 (CA19-9) tumor marker response, time to progression, overall survival and toxicity. RESULTS: A median of 3 treatment cycles (range 1-36) was given to 39 patients. After a median follow-up of 6.6 months, 27 patients were evaluable for response: no complete or partial responses were observed, but 15 patients (39%) had stable disease. A CA19-9 reduction of >20% after 2 cycles of Cap was documented in 6 patients (15%). Median time to progression was 2.3 months (range 0.5-45.1) and median overall survival (since start of Cap treatment) was 7.6 months (range 0.7-45.1). Predominant grade 2 and 3 toxicities (per patient analysis) were hand-foot syndrome 28% (13% grade 3); anemia 23%; leg edema 15%; diarrhea 13%; nausea/vomiting 10%, and leukocytopenia 10%. CONCLUSION: Single-agent Cap is a safe treatment option for Gem-pretreated patients with advanced PC. Further evaluation of Cap in controlled clinical trials of Gem-pretreated patients with advanced PC is recommended.