pazopanib and Carcinosarcoma

Gastric carcinosarcoma is most frequently diagnosed at an advanced stage when the tumor is generally large with invasion into other organs, lymph node metastasis, and distant metastasis. Standard chemotherapy has not been established, and surgery is the only curative treatment. Here, we present a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib.. A 77-year-old man was referred to our hospital because of nausea and vomiting. Computed tomography and upper gastrointestinal endoscopy revealed a type 1 tumor arising from the gastric antrum and extending into the duodenal bulb. He underwent distal gastrectomy (D2) with Roux-en-Y reconstruction. Histopathologically, the tumor had mixed adenocarcinoma and sarcoma components. According to the tumor-node-metastasis classification, the diagnosis was primary gastric carcinosarcoma pT1bN1M0 stage IB. Liver metastasis was detected 2 months after surgery; multiple lung metastases were detected 17 month after surgery. A genomic profiling test was performed using liver specimens as the patient became refractory to chemotherapy commonly used for gastric cancer, and the test revealed FGFR2 amplification along with TP53 R209*, AKT3 N127D, NOTCH1 A2036T, and POLD1 M161I. The patient was treated with pazopanib (800 mg/daily), and the tumor growth was controlled for 11 months.. We report a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. This case suggested that pazopanib may be effective in treating gastric carcinosarcoma.

Topics: Aged; Carcinosarcoma; Gastrectomy; Humans; Indazoles; Male; Pyrimidines; Receptor, Fibroblast Growth Factor, Type 2; Stomach Neoplasms; Sulfonamides

Carcinosarcomas of the female genital tract, also called malignant mixed müllerian tumors, are aggressive biphasic tumors. Second-line treatment options in the recurrent/persistent setting have yielded marginal responses. Given the potential role of angiogenesis in the gynecological carcinomas, pazopanib, a VEGFR inhibitor, was investigated in the management of patients with recurrent carcinosarcoma of the uterus.. Eligible patients had histologically confirmed carcinosarcoma of the uterus, a maximum of two prior lines of therapy, adequate renal, hepatic and hematologic function and a performance status of 0-2. Pazopanib was administered orally at 800mg. Two dose reductions were allowed. The primary objective was to ascertain the activity of pazopanib as measured by the proportion of patients who survive progression-free for at least six months and the proportion of patients that have objective tumor responses. Secondary objectives included the frequency and severity of adverse events as assessed by CTCAE v4.0.. Of the 22 enrolled patients, 19 were eligible and evaluable for toxicity and survival. No patients had a partial or complete response (90% confidence interval [CI]: 0%, 14.6%). Three patients (15.8%) had PFS ≥6months (90% CI: 4.4%, 35.9%). The median PFS was 2.0months (first and third quartiles were 1.6 and 4.0months, respectively). The median overall survival was 8.7months (first and third quartiles were 2.6 and 14.0months, respectively).. Pazopanib demonstrated minimal activity as a second or third line treatment for advanced uterine carcinosarcoma. Potential clinical trial participation should be discussed with the patients.

Topics: Aged; Angiogenesis Inhibitors; Carcinosarcoma; Disease-Free Survival; Female; Humans; Indazoles; Middle Aged; Mixed Tumor, Mullerian; Neoplasm Recurrence, Local; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Sulfonamides; Treatment Outcome; Uterine Neoplasms

Carcinosarcoma is a rare cancer, and its prognosis is poor. There are few reports on the prognostic factors of patients with carcinosarcoma who receive second-line chemotherapy.. To investigate the outcome and prognostic factors of patients who received second-line chemotherapy for gynecologic carcinosarcoma.. We retrospectively investigated patients with ovarian or uterine carcinosarcoma, who were treated at two institutions from July 2006 to March 2018. All patients who had received second-line chemotherapy for advanced or recurrent disease were eligible. The efficacy of second-line chemotherapy and prognostic factors were evaluated.. Forty-six patients were eligible. Combination chemotherapy was used in approximately half (52.2%) of the patients. The response rate and disease control rate of second-line chemotherapy were 32.6 and 60.9%, respectively. The median follow-up period was 11.0 (range, 8.8-107.5) months. The median progression-free survival and overall survival were 6.3 (95% CI, 3.2-7.5) months and 12.9 (95% CI, 7.8-16.0) months, respectively. In the multivariate analysis of overall survival, a treatment-free interval >180 days was a significant good prognostic factor. The median overall survival was 7.8 (95% CI, 5.1-10.5) months in the <180 days group and 16.4 (95% CI, 13.1-130.6) months in the >180 days group (p = 0.0052; hazard ratio, 0.26; 95% CI, 0.10-0.66), respectively.. The outcome of gynecologic carcinosarcoma in the second-line setting is poor, especially in patients with a short treatment-free interval.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinosarcoma; Docetaxel; Doxorubicin; Female; Humans; Ifosfamide; Indazoles; Middle Aged; Ovarian Neoplasms; Paclitaxel; Prognosis; Progression-Free Survival; Pyrimidines; Retrospective Studies; Sulfonamides; Treatment Outcome; Uterine Neoplasms

Pulmonary carcinosarcoma (PCS) is a rare primary lung malignancy and has a poor prognosis among lung tumor histological subtypes. However, an appropriate treatment strategy has not been developed for unresectable PCS.. A 65-year-old man who was diagnosed with PCS was treated by surgical removal of the primary lung lesion, followed by six cycles of adjuvant chemotherapy with cisplatin plus irinotecan. Following the chemotherapy, he experienced a relapse with brain metastasis, which induced the rapid onset of left leg paralysis. Radical surgical resection and stereotactic radiosurgery to the resection cavity were performed. However, meningeal dissemination and new lung metastases occurred after a year and half. To control these multiple metastatic lesions, the patient was treated with the multiple kinase inhibitor pazopanib. No change was observed in the meningeal dissemination, while the metastatic lung lesions were prominently reduced in size following treatment with pazopanib. Consequently, the patient showed a partial response to pazopanib treatment, although the dose of pazopanib was reduced by half as a result of thrombocytopenia.. This is the first report of metastatic PCS showing an evident therapeutic response to tumor-targeted therapy. We suggest that pazopanib may be a therapeutic option for patients with metastatic PCS.

Topics: Aged; Angiogenesis Inhibitors; Antineoplastic Agents; Brain Neoplasms; Carcinosarcoma; Chemotherapy, Adjuvant; Dose-Response Relationship, Drug; Humans; Indazoles; Lung Neoplasms; Male; Meningeal Neoplasms; Neoplasm Staging; Pneumonectomy; Pyrimidines; Radiosurgery; Sulfonamides; Thrombocytopenia; Treatment Outcome

Topics: Aged; Antineoplastic Agents; Carcinosarcoma; Female; Humans; Indazoles; Middle Aged; Ovarian Neoplasms; Pyrimidines; Sulfonamides; Tomography, X-Ray Computed; Uterine Neoplasms