Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

Capecitabine/cisplatin doublet in anthracycline and taxane pretreated and HER-2 negative metastatic breast carcinoma patients.

PURPOSE: To evaluate the activity and toxicity of the combination of capecitabine and cisplatin (CapCisp) in anthracycline- and taxane-pretreated HER-2 negative metastatic breast carcinoma (MBC) female patients. METHODS: Patients with HER-2 negative MBC pretreated with anthracycline and taxane and who were then treated with CapCisp combination were retrospectively evaluated. All patients received Cap 1000 mg/m(2) on days 1-14, and Cisp 60 mg/m(2) on day 1, repeated every 3 weeks. In case of disease control without severe toxicity, single agent Cap was continued until progression or unacceptable toxicities after Cisp cessation. RESULTS: Sixty-four MBC patients with median age 43 years (range 20-66) were included the study. Infiltrative ductal carcinoma prevailed (85.9%). Ten percent of the patients had grade I, 42% grade II, and 48.0% grade III tumors. Estrogen receptor (ER) and progesterone receptor (PR) were positive in 48.4 and 51.6% of the patients, respectively. Twenty-eight percent of the patients had triple negative tumors. Almost the entire patient group had this regimen as a third-line treatment. The median combination chemotherapy cycles were 6 (range 2-8). Twenty-seven non-progressive patients continued treatment with single-agent Cap. Median single-agent Cap cycles after the combination chemotherapy were 4 (range 1-38). Disease control rate was 81.3% (complete response 6.3%; partial response 48.4%, stable disease 26.6%, progressive disease 18.8%). Median follow-up time was 10.6 months. Median time to disease progression was 7 months, median overall survival (OS) was 17 months (95% CI, 6.9-16.1) measured from the start of CapCisp chemotherapy. There were no treatment-related deaths. The most frequent grade 3-4 toxicities were neutropenia (8.1%), nausea - vomiting (7.8%) and thrombocytopenia (6.3%). CONCLUSION: CapCisp doublet has an encouraging antitumor activity with acceptable and manageable toxicity in anthracycline- and taxane-pretreated HER-2 negative metastatic breast carcinoma patients.

Duration of anti-HER2 blockage therapy may improve survival in HER2 positive metastatic breast carcinoma patients.

PURPOSE: The duration of anti-HER2 blockage therapy in metastatic breast cancer patients is still unclear. We aimed to evaluate the effect of the anti-HER2 blockage therapy duration and other factors on survival in HER2 positive metastatic breast carcinoma (MBC) patients. METHODS: The medical records of 193 HER2 positive MBC patients, who did not have the opportunity to receive adjuvant trastuzumab therapy but had received trastuzumab in the metastatic setting were retrospectively evaluated. RESULTS: The median age at diagnosis was 45.0 years (range 21-83). Ninety-two (47.7%) patients received palliative trastuzumab < 6 months median, whereas 101 patients received trastuzumab ≥ 6 months median. The median number of trastuzumab cycles was 8 (range 1-51). Median survival after breast cancer recurrence was 31.0 months (range 24.3-37.7). The duration of trastuzumab therapy had a significant impact on the prognosis of recurrent breast cancer (22.0 vs 49.0 months, for ≤ 6 months of treatment duration, respectively; p<0.0001). Survival after breast cancer recurrence for the patients who received lapatinib plus capecitabine vs those who did not was significantly different (59 patients, p=0.005). Moreover, there was a statistically significant relationship between prolonged lapatinib plus capecitabine combination therapy and improved survival after disease recurrence (p=0.022). In the multivariate Cox regression analysis, treatment with trastuzumab > 6 months (p=0.003) was the only independent prognostic factor for survival after breast cancer recurrence. CONCLUSION: The duration of anti-HER2 blockage therapies, especially with trastuzumab, seems to improve survival of HER2-positive metastatic breast cancer patients who were not previously treated with adjuvant trastuzumab, regardless of other therapies.

What is the best treatment option in postmenopausal, hormone responsive breast cancer patients with isolated bone metastases?

BACKGROUND: Bone is the most common metastatic site for breast cancer. AIM: To determine the effectiveness of addition of chemotherapy to hormonal therapy in postmenopausal hormone receptor-positive breast cancer patients with isolated bone metastases. MATERIALS AND METHODS: Between June 2001 and January 2007, 101 patients were classified into two groups according to initial treatment modalities; patients who received hormonotherapy only (group I) and chemotherapy followed by hormonotherapy (group II). The effect of treatment choice on clinical course, time to progression, and overall survival were evaluated. RESULTS: There were 70 patients in group I and 31 patients in group II. Bone metastases in 27 patients (26.7%) were synchronous and the remainder were metachronous. The median follow-up time was 41 months. The two groups showed similar results when patients' tumor characteristics were compared. However, 81% of synchronous cases had upfront chemotherapy following hormonotherapy, whereas this ratio was only 12% in the metachronous group. All patients received systemic antiresorptive bisphosphonates whereas only 24 patients required palliative radiotherapy at some time during the course of their disease. In groups I and II, the median time to progression was 12 and 16 months (P: 0.96) and median overall survival was 41 and 40 months (P: 0.79), respectively. In HER-2-positive patients, a trend of prolongation of overall survival was observed in group II, but it was not statistically significant (P: 0.12). CONCLUSIONS: Anti-hormonal therapy still seems to be considered as the ideal treatment of choice for postmenapousal breast cancer patients with isolated bone metastases.

Multiple primary malignant neoplasms: multi-center results from Turkey.

PURPOSE: Multiple primary malignant neoplasms (MPMNs) are defined as a diagnosis of two or more indepen-dent primary malignancies of different histologies/origins in an individual. The frequency of MPMN is being increasing. In this study we aimed to determine the frequency and clinical features of second primary cancers (SPCs). METHODS: From January 1990 to December 2010, patients with MPMNs were screened in 5 centers. Data were obtained retrospectively from hospital charts. RESULTS: Three hundred seventy-seven patients with MPMNs were evaluated. The median age at initial cancer diagnosis was 61 years (range 18-88). The median age at second cancer was 64 years (range 20-89). The median time between two cancer diagnoses was 15 months (range 0-504). Male to female ratio was 1.44 (M/F 223/154). The most frequent initial cancer types were head and neck (54 patients, 14.3%), breast (54 patients, 14.3%), and colorectal (43 patients, 11.4%). The most frequent second cancer types were lung (76 patients, 20.2%), colorectal (39 patients, 10.3%) and breast (33 patients, 8.8%). The most common cancer pairs in females were breast-gynecologic cancers (15 patients, 9.7%), colorectal-breast cancers (9 patients, 5.8%) and breast-colorectal cancers (7 patients, 4.5%). The most common cancer pairs in males were head and neck-lung cancers (29 patients, 13%), bladder-lung cancers (9 patients, 4%), and bladder-prostate cancers (7 patients, 3%). The median follow up was 36 months (range 17horbar;595). CONCLUSION: Physicians should be aware of SPCs probabilities. Newly developed suspicious lesions should be evaluated rigorously. Histopathologic evaluations of suspicious lesions for second tumors should be used extensively if needed. In our series, the most common pairs were breast-gynecologic cancers in females and head and neck-lung cancers in males.

Adjuvant therapy for gallbladder and bile duct cancers: retrospective comparative study.

PURPOSE: To study the efficacy of adjuvant therapy (chemotherapy and radiotherapy) in early stages (I-III) of gallbladder and bile duct cancers. METHODS: The clinical and pathological characteristics, treatment details and survival data of patients operated with early stages (I-III) of gallbladder and bile duct cancers and followed up in our clinic between August 2002 - November 2009 were retrospectively evaluated. RESULTS: 52 patients (median age 64 years) with early stages of gallbladder (n=36) and bile duct (n=16) cancers were analysed. Twenty-three (44.2%) patients had stage I, 23 (44.2%) stage II, and 6 (11.5%) stage III cancers. Approximately half of the patients (n=25; 48.1%) received postoperative adjuvant chemotherapy and/or radiotherapy. Patients with adjuvant treatment were younger than those without (62 vs. 71 years, p=0.06). Eighteen patients received chemotherapy alone, 2 chemotherapy followed by radiotherapy, 1 chemotherapy concurrently with radiotherapy, and 4 radiotherapy alone as adjuvant therapy. The regimen most frequently used (57.1%) was CFF (cisplatin 50 mg/m(2), day 1; folinic acid 200 mg/m(2), day 1; 5-fluorouracil [5-FU] 400 mg/m(2) bolus day 1 and 1600 mg/m(2) 48h continuous infusion). Some poor prognostic factors like high tumor grade and vascular invasion were more frequent in patients who received adjuvant therapy. The median disease free survival (DFS) was 11.4 months for the patients that received adjuvant therapy vs. 8.2 months for those without adjuvant therapy (p=0.67). During follow up 11 patients (44.0%) with adjuvant therapy and 12 (44.4%) without have died (p=0.97). The estimated median survival was 29 months. CONCLUSION: Although previous studies had shown that 5-FU-based adjuvant chemotherapy may provide a small survival advantage, this was not confirmed in the present study. Prospective adjuvant trials with a standard chemotherapy regimen and larger numbers of patients are required.

Safety and efficacy of FOLFIRI-bevacizumab for metastatic colorectal carcinoma as second line treatment.

PURPOSE: To evaluate the efficacy and the safety of FOLFIRI-bevacizumab (B) in the 2nd line therapy of metastatic colorectal carcinoma (MCRC). METHODS: Between March 2006 and July 2009 35 patients with MCRC were treated with 2nd line therapy FOLFIRI- B (irinotecan 180 mg/m(2) D1, folinic acid 200 mg/m(2) D1, 5-fluorouracil/5 FU 400 mg/m(2) bolus D1, followed by 5 FU 2600 mg/m(2) 46-h continuous infusion, and bevacizumab 5 mg/kg D1, every 2 weeks) Their data were collected and analysed. RESULTS: The patient median age was 54 years (range 36-75). One patient (2.8%) had received oxaliplatin-based adjuvant chemotherapy and 33 patients (94.3%) were exposed to oxaliplatin during first line chemotherapy for MCRC. The median follow up period was 12.2 months (range 1.5-37.9). Complete remission (CR) was achieved in 5.7% of the patients and the sum of CR and partial remission (PR) was 11.4%. Disease control (CR+PR+stable disease/SD) was registered in 74.3% of the patients. During follow up, progression (PD) was seen in 32 (91.4%) patients and 23 (65.7%) patients had died. The median progression free survival (PFS) was 7.4 months (95%CI 5.5-9.3) and the median overall survival (OS) 13 months (95%CI 8.8-17.2). Grade 3-4 toxicity requiring delay of chemotherapy was observed in 12 (34.3%) patients with 10 patients (28.6%) having neutropenia and 2 (5.7%) diarrhea. CONCLUSION: FOLFIRI-B may be an efficient and safe choice in the 2nd line treatment of patients with MCRC previously treated with oxaliplatin.

First-line therapy for metastatic colorectal carcinoma: modified FOLFOX4 or FOLFIRI-bevacizumab.

PURPOSE: The aim of this study was to compare the efficacy and toxicity of modified (m) FOLFOX4 (folinic acid, 5-fluorouracil [5-FU], and oxaliplatin) vs. FOLFIRI-B (folinic acid, 5-FU, irinotecan, and bevacizumab) as first-line treatment of metastatic colorectal carcinoma (MCRC). METHODS: The medical records of 89 MCRC patients treated with either mFOLFOX4 (group 1) or FOLFIRI-B (group 2) as first-line chemotherapy were evaluated retrospectively. RESULTS: Complete (CR) plus partial response (PR) were seen in 18 (36.7%) vs. 13 (32.5%) patients in the mFOLFOX4 vs. FOLFIRI-B, respectively (p=0.67). Median progression-free survival (PFS) was 9 months (95% CI 7.2- 9.5) vs. 10 months (95% CI 7.6-12.3) in group 1 vs. group 2, respectively (p=0.30). Median overall survival (OS) was 22 months (95% CI 17.6-26.3) and 19 months (95% CI 13-24.9) in group 1 and 2, respectively (p=0.32). There was no statistically significant difference in grade 3-4 hematological toxicity between the groups, but grade 3-4 grade weakness, diarrhea, nausea and vomiting was observed more frequently in the FOLFIRI-B patients (p=0.03, p=0.01, p=0.05, respectively). CONCLUSION: Our data suggest that mFOLFOX4 and FOLFIRI-B are equally effective as first-line chemotherapy in MCRC patients. This may partially be explained by the fact that almost 50% of those receiving FOLFOX in the first-line received FOLFIRI-B in the second-gline, an observation suggesting that bevacizumab in the second line may be as effective as in the first line.

Concomitant Hodgkin's lymphoma and gastric adenocarcinoma: a rare coincidence.

Gastric adenocarcinomas may be seen together with colon, prostate, breast, liver, lung and gynecological malignancies as synchronous or metachronous cancer. However, Hodgkin's lymphoma (HL) is rarely diagnosed with solid tumors. Herein, a 72-year-old man with both gastric adenocarcinoma and HL has been presented. Mass lesions far away from the primary tumor in cancer patients can be not only the sign of distant metastasis but also another primary malignancy. In the English literature, synchronous gastric adenocarcinoma and HL has been rarely reported, and as far as we know, this is the third case to be reported.

Good tolerance of weekly irinotecan in a patient with metastatic colorectal cancer on chronic hemodialysis.

Pharmacokinetic properties of many antineoplastic agents or their metabolites change with organ dysfunction. Unfortunately, chemotherapy doses determined in phase I and II studies in patients with normal hepatic and renal reserves are not usually applicable to those with hepatic and/or renal dysfunction. Considering the high incidence of colorectal adenocarcinoma, it is not unusual for a colorectal cancer patient to be on chronic hemodialysis. We report a patient with metastatic colorectal cancer on chronic hemodialysis who tolerated weekly irinotecan at 50 mg/m2 well without significant toxicity. We briefly discuss therapeutic dose modification in such patients.

Squamous cell carcinoma of the tongue in a patient with Fanconi's anemia: a case report and review of the literature.

Fanconi's anemia (FA) is an autosomal recessive disorder characterized by constitutional aplastic anemia and congenital abnormalities. Patients with this disorder are prone to develop leukemia. Besides the risk of squamous cell carcinoma (SCC), development especially in the head and neck region is also increased. Up to now 40 patients with FA have been reported to develop SCC, and in 14 of them the tongue was the primary site. All of the reported SCC in FA patients originated in mucosal and mucocutaneous sites, especially oral (n=25) and anogenital sites (n=8) and the esophagus (n=6), with the exception of two patients with multiple cutaneous involvement. We report a new case of SCC of the tongue in a patient with FA and review the previous SCC cases.

Blue rubber bleb nevus syndrome.

A 26-yr-old man was admitted with malaise and melena. During the physical examination, six hemangiomas were spotted on the skin, and laboratory evaluations proved the existence of severe iron deficiency anemia (Hb 2.9 g/dl). Upper endoscopy and small bowel follow-through revealed no pathology. Colonoscopy documented the presence of a blue-red cavernous hemangioma, 1 cm in diameter, at the splenic flexura. The skin and colonic lesions were typical; thus, blue-rubber-bleb-nevus syndrome was diagnosed. The patient was given blood transfusions followed by oral iron supplementation. He refused further evaluation or surgery and is still fine after a follow-up period of 6 months. Here, we present a discussion of this case, together with a detailed review of the literature.