Tiago Kenji Takahashi

A multicenter, multinational analysis of mitomycin C in refractory metastatic colorectal cancer

BACKGROUND A considerable number of metastatic colorectal cancer (mCRC) patients who progress on standard treatment with 5-fluorouracil (5FU), oxaliplatin, irinotecan and monoclonal antibodies, still have adequate performance status and desire further treatment. Mitomycin C (MMC) has been widely used in this context, and despite good tolerability, there are doubts regarding its true benefit. METHODS In order to assess the activity of MMC in the refractory mCRC setting, we retrospectively evaluated 109 heavily pre-treated patients who received MMC as single agent or in combination for mCRC at three different institutions in two countries. RESULTS Median patients age was 54 years old, 57% were male and 94% had performance status ECOG 0 or 1. MMC was used in second line in 11%, third line in 38% and fourth line or beyond in 51% of patients. 58% received MMC combinations, mainly with capecitabine. Grade 3 or 4 toxicity was observed in 5% of patients and 6% required dose reductions. Median time to treatment failure (TTF) was 1.7 months with MMC and 3.6 months on the regimen prior to MMC, with a ratio between these TTF below 1 in 82% of patients. Median survival was only 4.5 months (95% confidence interval (CI) of 3.48-5.56). CONCLUSIONS This retrospective data represent the largest reported series of unselected refractory mCRC patients treated with MMC. The median survival of 4.5 months is similar to the survival expected for best supportive care. This lack of activity strongly suggests that MMC should not be routinely used in refractory mCRC.

Primary Ovary Choriocarcinoma: Individual DNA Polymorphic Analysis as a Strategy to Confirm Diagnosis and Treatment:

Abstract Primary choriocarcinoma of the ovary is rare. Furthermore, this tumor can arise from gestational tissue or pure germ cells of the ovary, with the latter resulting in non-gestational choriocarcinoma. While the clinical characteristics and histology of both tumor types are identical, differentiation of these tumors is necessary for effective treatment. One strategy for the differentiation of these tumors types is to assay for the presence of paternal DNA. Accordingly, in the present case, a patient with primary choriocarcinoma of the ovary with a non-gestational origin was confirmed by DNA analysis. The patient subsequently exhibited an excellent response to chemotherapy, and following surgery, achieved complete remission. A pathological analysis of surgical specimens further confirmed the absence of tumor.

Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A Retrospective Analysis

Purpose Extensive-stage small-cell lung cancer (esSCLC) is an incurable disease and represents a therapeutic challenge because of its poor prognosis. Studies in prophylactic cranial irradiation (PCI) in esSCLC have shown a decreased incidence of symptomatic brain metastases in patients who respond to systemic chemotherapy. However, its effect on overall survival is debatable. We evaluated the benefit of PCI in patients with esSCLC in terms of overall survival, progression-free survival, incidence of brain metastases, recurrence rate, and exposure to postrecurrence therapies. Materials and Methods We retrospectively reviewed electronic charts from patients diagnosed with esSCLC from 2008 to 2014 at our institution. All patients had negative baseline brain imaging before chemotherapy and PCI and received at least 4 cycles of platinum-based chemotherapy in the first-line setting without progressive disease on follow-up. PCI was performed at the discretion of the treating physician. Analyses were based on descriptive statistics. Survival curves were calculated by Kaplan-Meier method. Results Among 46 eligible patients, 16 (35%) received PCI and 30 (65%) did not. Compared with no PCI, PCI led to improved progression-free survival (median, 10.32 v 7.66 months; hazard ratio, 0.4521; 95% CI, 0.2481 to 0.8237; P < .001) and overall survival (median, 20.94 v 11.05 months; hazard ratio, 0.2655; 95% CI, 0.1420 to 0.4964; P < .001) as well as lower incidence of brain metastases (19% v 53%; P = .0273) and higher exposure to second-line chemotherapy (87% v 57%; P = .0479). Conclusion Careful patient selection for PCI can improve not only brain metastases control and higher second-line chemotherapy exposure but also patient survival.

Palliative chemotherapy outcomes in patients with ECOG-PS higher than 1

Purpose Although patients with incurable disease and Eastern Cooperative Oncology Group performance status (ECOG-PS ≥ 2) are underrepresented in clinical trials, they are frequently offered palliative chemotherapy (pCT) in daily clinical practice in order to improve symptoms and quality of life. In this case-control retrospective analysis, our goal was to identify factors associated with poorer survival and lack of benefit of pCT in this population. Patients and methods We evaluated 2,514 patients who died between August 2011 and July 2012 in an academic cancer care institution and its hospice. A total of 301 patients with solid tumours and ECOG-PS ≥ 2 at prescription of pCT were selected for this case-control retrospective analysis. Cases were defined as patients who survived less than 90 days after the first cycle of first line pCT, and controls were those who had a longer survival. Results 142 cases and 159 controls were included. Cases were more likely to experience grade ≥ 3 toxicity (43% versus 28%; p = 0.005), die of toxicity (16% versus 6%; p < 0.001) and not be offered best supportive care (BSC) only (47% versus 71%; p < 0.001). Median overall survival was 204 among controls and 34 days in cases (hazard ratio = 0.177; 95%, confidence interval = 0.015–0.033, p < 0.001). Logistic regression analysis identified ECOG-PS > 2 (odds ratio (OR) = 2.3, p = 0.044) and serum creatinine (sCr) > 1 mg/dL (OR = 11.2, p < 0.001) as independent predictors of 90-day mortality. Conclusions The independent predictors of short survival (less than 3 months) after initiation of pCT in this population were ECOG-PS > 2 and elevated sCr. Therefore, patient selection is crucial, as pCT may be deleterious in ECOG-PS ≥ 2 pts.

Multiagent chemotherapy for metastatic adenocarcinoma of the seminal vesicle.

Adenocarcinoma of the seminal vesicle is a rare condition, with fewer than 60 cases described in the literature. Most reports highlight the histopathological characteristics of the tumor; however, the role of chemotherapy, especially in the metastatic setting, is poorly described. In this paper, we describe a patient with metastatic disease, who sustained a response to modified FOLFOX6 as first-line therapy. This platinum-based combination therapy seems effective in this scenario and may provide an opportunity for extended survival and relief of symptoms.

Metastatic Lung Adenocarcinoma Harboring an EGFR-Activating Mutation in a Heart Transplant Recipient

In March 2016, this patient presented with symptoms of cough, weight loss, hyporexia, and dyspnea. Initial work-up demonstrated a 3.13 2.3–cm posterior left upper lobe mass, multiple bilateral lung micronodules, as well as several enlarged lymph nodes (ipsilateral hilum, bilateral upper paratracheal, and para-aortic sites). Pulmonary transbronchial biopsy revealed an adenocarcinoma(Fig1). F-labeled fluorodeoxyglucosepositron emission tomography showed increased uptake in primary mass, enlarged lymph nodes, and lymphangitic carcinomatosis (T2aN3M1a).

Malignancy-Related Hypercalcemia in Advanced Solid Tumors: Survival Outcomes

Purpose Malignancy-related hypercalcemia (MRH) is associated with a dismal prognosis. The widespread use of bisphosphonates (BPs), availability of more effective drugs in cancer treatment, and improvement in supportive care might have attenuated its impact. Patients and Methods To assess overall survival (OS) of patients with MRH in a contemporary setting, we conducted a retrospective analysis of 306 patients with solid cancer hospitalized for symptomatic hypercalcemia. A multivariable Cox proportional hazards regression model was performed to evaluate possible prognostic factors associated with MRH. Results All patients had serum ionized calcium > 5.5 mg/dL or total Ca > 10.5 mg/dL. Median age was 57 years, and the majority had squamous cell carcinoma (62%) and Eastern Cooperative Oncology Group performance status > 1 (96%). Head and neck was the most frequent primary site (28%). Forty-five percent had no previous chemotherapy (CT), and subsequent CT was administered to 32%. Eighty-three percent received BP with no survival gain. Median OS was 40 (95% CI, 33 to 47) days. Patients with a performance status > 2, altered mental status, C-reactive protein > 30 mg/L, albumin < 2.5 g/dL, or body mass index < 18 kg/m2 had significantly poorer survival in a univariable analysis, and longer OS was related to treatment-naive patients, subsequent CT, and breast primary site. In the multivariable analysis, subsequent CT led to a median OS improvement of 144 versus 25 days (hazard ratio, 0.24; 95% CI, 0.14 to 0.40; P < .001). Conclusion In a contemporary setting, MRH remains a marker of poor prognosis. Patients treated with CT had better survival, which suggests that appropriate treatment of selected patients might alter the course of this syndrome.

Advanced small-cell ovarian carcinoma, hypercalcemic type: a challenging therapeutic entity

Small-cell ovarian carcinoma (SCOC) is a rare and aggressive neoplasia, predominantly affecting young women who are frequently first diagnosed with advanced stage disease. Platinum-based chemotherapy (ChT) can provide high response rates and rapidly ameliorate symptoms in this scenario. However, progression after chemotherapy usually occurs quickly, leading to high mortality rates. In addition, ChT complications, such as tumor lysis syndrome (TLS) can also occur, jeopardizing the patient’s outcome. We present a case of metastatic SCOC in a 47-year-old patient who achieved tumor response after platinum-based chemotherapy and developed TLS, from which she recovered with supportive treatment. After the second ChT cycle, she developed febrile neutropenia and died 8 weeks after the diagnosis of SCOC. Although SCOC is a chemo-sensitive tumor, short-lived responses and frequent chemotherapy complications lead to a dismal prognosis.

A multicenter, multinational retrospective analysis of mitomycin C (MMC) in refractory metastatic colorectal cancer (mCRC).

3577 Background: A considerable number of mCRC patients (pts) who progress on standard treatment with 5-fluorouracil (5FU), oxaliplatin, irinotecan and monoclonal antibodies still have good performance and desire further treatment. MMC has been widely used in this situation, and despite good tolerability, there is no agreement on its role. METHODS In order to assess the activity of MMC in the refractory mCRC setting, we retrospectively evaluated 109 heavily pre-treated pts who received MMC as single agent or in combination for mCRC at three different institutions. RESULTS Of the 109 pts, 30 (27.5%) were treated at M. D. Anderson Cancer Center (USA); 55 (50.5%) at Hospital Sírio Libanês (Brazil) and 24 (22%) at Instituto do Câncer de São Paulo (Brazil). Median age was 54 years old, 57% were male and 94% were performance status ECOG 0 or 1 at diagnosis. MMC was used in second-line in 11%, third-line in 37.6% and fourth-line or beyond in 51.4% of pts. Median TTF on the regimen prior to MMC therapy was 3.7 months. 42% received MMC as single agent while 58% received MMC combinations, mainly with fluoropyrimidines (49%). Severe toxicity was rare (1.8%), with dose reductions in 6.4% of pts. Clinical benefit with MMC, defined as improved symptoms by clinician assessment, was 12%. By response criteria, no radigraphic responses were seen. Median survival was only 4.6 months (95% CI of 4.1 to 5.5). CONCLUSIONS This retrospective data represents the largest reported series of refractory mCRC patients treated with MMC. There were no patients with radiographic response and the low clinical benefit rate is not consistent with an active regimen. The median survival of 4.6 months is similar to the median survival expected for best supportive care in the refractory setting (4.5 months). This lack of activity strongly suggests that mitomycin should not be used in refractory mCRC.