Hüseyin Abalı

Promising efficacy of sorafenib in a relapsed thymic carcinoma with C-KIT exon 11 deletion mutation

Advanced thymic carcinoma (TC) is a very aggressive disease. To date there are no established treatment options for the refractory and recurrent disease and only a few prospective trials have been conducted in patients with TC. Here we present a case of a relapsed TC patient, who, by using combination chemotherapy, showed a positive response to sorafenib with C-KIT exon 11 mutation.

The efficacy and safety of reduced-dose docetaxel, cisplatin, and 5-fluorouracil in the first-line treatment of advanced stage gastric adenocarcinoma.

Patients with advanced gastric carcinoma have still had bad prognosis despite advances in the modern treatment era. Docetaxel, cisplatin, 5-fluorouracil (DCF) is effective, but highly toxic regimen for advanced cases. In this study, we modified the standard doses of DCF (mDCF) to evaluate the effectiveness and side effects. From July 2005 to July 2008, 37 advanced gastric cancer patients treated with at least one course of mDCF protocol as first-line treatment were included. The mDCF protocol included 60xa0mg/m2 docetaxel and cisplatin for 1xa0day and 600xa0mg/m2/day, 5-flourouracil infusion for 5xa0days, repeated every 3xa0weeks. No patients used prophylactic granulocte -colony stimulating factor. Of the patients, 28 were male and nine were female; the median age was 53 (23–65) years. Of them, 83.8% received at least four courses of chemotherapy and 64.9% completed the preplanned six courses of treatment. Eleven (29.7%) of those patients who received mDCF in the first-line treatment used the FOLFIRI (5-FU, folinic acit, irinotekan) regimen for the second-line treatment. Response rates were evaluated according to RECIST criteria in 30 out of 37 patients. The median follow-up time was 7.1xa0months. The longest follow-up time was 19.9xa0months. Two patients (5.4%) had complete response, nine (21.6%) had partial response, and 14 (37.9%) had stabilized disease; overall, the disease was controlled in 25 patients (64.9%) whereas five patients (13.5%) had progression. Median time to progression was 6.7xa0months and overall survival was 10xa0months. The assessment of patients for grade 3–4 toxicity revealed that while 5.4% had anemia and 8.1% had neutropenia, 5.4% nausea and 5.4% diarrhea. Neutropenic fever developed in two patients, requiring hospitalization. G-CSF was used in three patients. Two patients with neutropenic fever and two with severe anemia (total number 4; 10.8%) received delayed chemotherapy. Dose reduction was required in four patients (10.8%), one due to neutropenia, one due to nephrotoxicity, and two due to nausea. No patient died due to chemotherapy toxicity. This retrospective study suggested that mDCF might have comparable efficacy with classical DFC, with better toxicity profile. However, its small size and retrospective nature should be considered when interpreting the results.

It appears to be safe to start chemotherapy on the day of implantation through subcutaneous venous port catheters in inpatient setting

GoalsIt is generally recommended to wait for at least 24xa0h before starting chemotherapy after implanting venous port catheters (VPC). Our aim was to evaluate whether it is safe to start chemotherapy on the day of implantation.Patients and methodsOne hundred eighty patients who had to be given chemotherapy on the day of VPC implantation at our institution from June 2005 to April 2007 were included.Main resultsOf patients, 122 were male (67.8%) and median age was 55xa0years. Majority (133, 72.8%) had colon and gastric adenocancer. Median time to chemotherapy onset from VPC implantation was 102xa0min (minimum–maximum, 12–402). One hundred sixty-four (91.1%) received prolonged chemotherapy infusions beyond 48xa0h. No life-threatening acute complications like pneumothorax and hemothorax developed. In one patient extravasation (empty saline extravasation secondary to wrong insertion of the needle), in 17 (9.4%) pain, and in 41 (22.8%) minor bleeding as echymosis were seen. Thrombosis developed in 11 (6.1%). Reasons for VPC removal were thrombosis (2), sepsis (2), cellulitis (1), skin dehiscence (1), and patient will (1).ConclusionChemotherapy administration immediately after VPC implantation appears safe without increased acute and chronic complications in inpatient setting.

Comparison of Cisplatin-5-Fluorouracil-Folinic Acid versus Modified Docetaxel-Cisplatin-5-Fluorouracil Regimens in the First-Line Treatment of Metastatic Gastric Cancer

Objective: Prognosis of metastatic gastric cancer is poor and median survival is between 3 and 5 months. Response rates of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in first-line treatment have been found to be 20–25% in the English literature. It has been demonstrated that adding docetaxel to combination chemotherapy improved time to progression and overall survival. However, the toxicity rates of the docetaxel-cisplatin-5-FU protocol were high. In our study we compared efficacy and toxicity of cisplatin-5-FU-folinic acid (CFF) and modified docetaxel-cisplatin-5-FU (mDCF) regimens in the first-line treatment of metastatic gastric cancer. Patients and Methods: Between June 2004 and October 2008, 70 patients with previously untreated metastatic gastric cancer treated with CFF (n = 30) and mDCF (n = 40) were retrospectively evaluated in the study. Survival and toxicity data were compared. Results: Median age of the patients was 53 years (range 23–69). Forty-eight percent of the patients were male and 75.7% had an ECOG performance status of 0–1. Prognostic factors including age, ECOG performance status, histopathological grade, and number and sites of metastases were similar between the groups. Objective response rates (complete and partial response) were higher in the mDCF group (30.0 vs. 13.3%, p = 0.19). While toxicity was acceptable in both groups, the most common grade 3–4 toxicities were anemia in 3.3 and 5.0%, neutropenia in 20 and 7.5%, febrile neutropenia in 6.7 and 5.0%, and diarrhea in 3.3 and 5.0% in the CFF and mDCF groups, respectively. Median follow-up was 10.3 (1.5–59.6) months. During that period 90 and 97.5% of the patients were dead in the CFF and mDCF groups, respectively. Median time to progression was 4.4 (95% CI 1.8–7.0) and 6.2 months (95% CI 5.6–6.8) (p = 0.85), median overall survival was 6.5 (95% CI 1.8–11.2) and 8.7 months (95% CI 6.7–10.7) (p = 0.88) in the CFF and mDCF groups, respectively. Conclusion: The mDCF regimen has been found to be more favorable than the CFF regimen with an acceptable toxicity profile in the first-line treatment of metastatic gastric cancer.

Unilateral hand-foot syndrome: an extraordinary side effect of capecitabine.

Background: Hand–foot syndrome (HFS), the most common toxicity of capecitabine, is characterized by tingling, numbness, pain, erythema, dryness, rash, swelling, increased pigmentation, and/or pruritus of the palmar and/or plantar surfaces of the hands and/or feet. HFS is usually seen in both the hands and the feet, with varying severity. We have previously published a case report of dihydropyrimidine dehydrogenase (DPD) deficiency that manifested a variant of HFS. Case report: We report the case of a 65-year-old Turkish Cypriot male patient with advanced gastric cancer who developed pain, numbness, and reddening in his left palm and left sole 10 days after the fourth cycle of capecitabine at a dose of 1,000u2009mg/m2/day twice daily (BID) on days 1 to 14 every 21 days. On physical examination, he had unilaterally erythematous changes and skin scaling on his left sole and palm consistent with grade II HFS. After stopping administration of capecitabine and supportive management, the HFS resolved in a week’s time. Conclusions: To the best of our knowledge, this is the first case of capecitabine-induced unilateral HFS. Further investigation related to this toxicity associated with capecitabine is warranted.

Who benefits most from adjuvant interferon treatment for melanoma

Metastatic melanoma has a poor prognosis; the median survival for patients with stage IV melanoma ranges from 8 to 18 months after diagnosis. Interferon-α provides significant improvement in disease-free survival at the cost of poor tolerability. Identifying patients who benefit the most may improve the cost:benefit ratio. In addition, no data exist for the role of adjuvant therapy in noncutaneous melanoma. Molecular profiles may help to identify patients who benefit the most from adjuvant interferon therapy. In this review, the American Joint Commission on Cancer 2009 staging criteria and emerging biomarker data to guide adjuvant treatment decisions will be discussed. Several criteria to guide selection of patients are discussed in detail. These include Breslow thickness, number of positive lymph nodes, whether or not the primary lesion has ulcerated, immunologic markers, and cytokine profiles. Substantial progress has been made in deciding which patients benefit from interferon-α adjuvant therapy. Interferon-α is the only agent currently approved for the adjuvant treatment of this deadly disease, despite its side effect profile. More effective drugs with better tolerability are needed.

Docetaxel, cisplatin, and fluorouracil combination in neoadjuvant setting in the treatment of locally advanced gastric adenocarcinoma: Phase II NEOTAX study

Erratum to: Cancer Chemother Pharmacol (2014), 74:1139–1147, DOI 10.1007/s00280‑014‑2586‑6. Unfortunately, the part of acknowledgement detail was omitted in the published article and the below line must be considered as the last sentence: This study is a Turkish Oncology Group trial.

Effect of port-care frequency on venous port catheter-related complications in cancer patients

PurposeSubcutaneous central venous port catheters (SCVPC) are of great importance in the treatment of patients with malignancies since they provide secure vascular access. Our aim was to assess the impact of long-term catheter care frequency on the frequency of port-related complications.Patients and methodsTwo hundred and seven patients who had not been on active chemotherapy through their SCVPC for at least 3xa0months were enrolled into the study. Those who received catheter care every 3xa0months or more frequently were assigned to the frequent care group, and the others to the infrequent care group. The patients were examined for port-related complications and thrombosis including port occlusion. Routinely in our clinic, catheter care was done by using 300xa0IU of heparin.ResultsAccording to the frequency of SCVPC care, 49 (23.7xa0%) patients were in the frequent care group and 158 (76.3xa0%) were in the infrequent care group. Median follow-up of all patients was 671xa0days (range 133–1712). Median frequency of port care in the frequent care group was 90xa0days (range 30–90), but 441.5xa0days in the infrequent care group (range 91–1630). None of the patients experienced port-related severe complications during the follow-up time. None of them presented with port occlusion. When the groups were analysed for thrombus (symptomatic and asymptomatic), there was no statistically significant difference (6.4 vs 13.8xa0%, pxa0=xa00.17). Those patients who had received more than first-line chemotherapy were found to have more thrombi than the patients who were treated with only one type of chemotherapy protocol (28.6 vs 10.2xa0%, pxa0=xa00.01), and the patients who had metastatic disease at the last control were found out to have thrombi more frequently than the non-metastatic patients (24.3 vs 9.3xa0%) (pxa0=xa00.01).ConclusionsIn the present study, there was no difference in port-related severe complications between frequent and infrequent care groups during follow-up. However, the rate of thrombosis was slightly higher in the infrequent port care group.

Severe systemic vasoconstriction starting with acute limb ischemia leading to death in a patient with well-differentiated pulmonary neuroendocrine carcinoma: A new paraneoplastic syndrome?

Severe systemic vasoconstriction starting with acute limb ischemia leading to death in a patient with well-differentiated pulmonary neuroendocrine carcinoma : axa0new paraneoplastic syndrome?

Little dose, huge toxicity: profound hematological toxicity of intrathecal methotrexate

A 60-year-old man presented with complaints of blurred vision and inability to raise the right eyelid 15 days after the last cycle of the planned six cycles R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) for stage IV follicular lymphoma. Complete remission was confirmed after the fourth cycle by positron emission tomography. On physical examination, he had third and fourth cranial nerve palsies, whereas the remainder of the neurological examination was unremarkable. Magnetic resonance imaging of cranium and orbital region with gadolinium enhancement were normal. Upon detection of lymphocytic infiltration in the cerebrospinal fluid (CSF) by cytology, isolated leptomeningeal relapse of follicular lymphoma was diagnosed without any sign of systemic relapse. Treatment with intrathecal methotrexate 12.5 mg twice a week was planned. After the second dose of the intrathecal methotrexate, he developed a grade IV neutropenia, grade IV thrombocytopenia and grade IV oral mucositis. Intrathecal chemotherapy was then stopped. He also developed neutropenic fever and had to receive prolonged antibiotic administration. Intrathecal chemotherapy withmethotrexate, Ara-C, or both with or without hydrocortisone is considered the standard of care for prophylaxis and treatment of central nervous system (CNS) lymphoma [1]. Although, intrathecal methotrexate can cause some neurological complications [2,3], it is quite unusual to observe grade IV hematological toxicity. To the best of our knowledge, profound hematological toxicity has not been reported. Intrathecal methotrexate is not altered by metabolic processes in the CSF and it passes through the systemic circulation slowly via choroid plexus [4]. Its metabolism after intrathecal administration probably resembles the one in the presence of large volume of ascitis or pleural effusions where it is redistributed to the systemic circulation slowly. Even the small amounts at 10–15 mg of intrathecal methotrexate which pass to the systemic circulation can therefore cause the myelosuppression and other feared methotrexate complications. Bruce et al. [5] showed in pediatric patients that systemic methotrexate exposure can be greater after intrathecal than oral route. Our patient had none of the unfavorable factors that predispose for methotrexate toxicity such as renal insufficiency, third spacing of fluid in the body, anatomic abnormality of CSF flow or a history of using albumin bound drugs. In summary, one should be aware that intrathecal methotrexate administration may cause some unexpected toxicities. To our knowledge, this is the first case of profound hematological toxicity reported after intrathecal administration of methotrexate in the adult literature.