levoleucovorin and Pseudomyxoma-Peritonei

The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients.. Patients with advanced colorectal cancer were treated with 5-FU [bolus (400 mg/m(2)) followed by a 22-h infusion (600 mg/m(2))] and LV (200 mg/m(2)) and escalating doses of SAM486A, 1-3-h infusion daily for 3 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of the combination. Twenty-seven patients with metastatic colorectal cancer and 1 with pseudomyxoma peritonei were treated. Twenty-six patients received SAM486A in the combination at doses ranging from 25 to 150 mg/m(2)/day. Dose-limiting toxicity consisting of fatigue grade 3 was seen at 150 mg/m(2)/day. Other adverse events included neutropenia, hand and foot syndrome, nausea, vomiting, diarrhea, and constipation. Fifteen of 26 patients evaluable for best response according to the Southwest Oncology Group criteria achieved a partial response [8 (30%) of 26] or stable disease [9 (35%) of 26]. SAM486A did not influence the pharmacokinetics of 5-FU, and SAM486A clearance was similar to that when used as a single agent.. The novel molecular agent SAM486A is tolerable and safe in combination with a standard 5-FU regimen in patients with advanced colorectal cancer. The dose of SAM486A recommended for additional studies with this combination is 125 mg/m(2)/day. A disease-directed evaluation of SAM486A using this regimen is warranted.

Topics: Adult; Aged; Amidines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Female; Fluorouracil; Humans; Indans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Pseudomyxoma Peritonei; Rectal Neoplasms; Treatment Outcome

A 52-year-old woman was referred to our department with multiple discharging sinuses and swelling in the right flank and iliac region for the past year. Ultrasound revealed a large collection in the right psoas muscle with the sinus tract reaching up to the skin in the right iliac region. Despite repeated attempts at drainage, the collection continued to increase in size. CT was requested and revealed a large heterogeneous irregular collection in the right psoas with fistulous communication with the cecum and skin with the erosion of the overlying ilium. Because of lack of vertebral involvement, enhancing internal septations, non-visualisation of the appendix and feculent material admixed with mucinous discharge from the sinus, pseudomyxoma retroperitonei secondary to ruptured mucinous neoplasm of the appendix was suspected. Mucoid material at the local site was sent for histopathology, which confirmed our suspicion. Our treatment plan after ileostomy was cytoreductive surgery along with adjuvant radiotherapy (40 Gy in 20 fractions) with chemotherapy (5-fluorouracil and folinic acid given for 30 weeks, once a week). However, after ileostomy, the patient refused further treatment, citing financial reasons.

Topics: Appendix; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Pseudomyxoma Peritonei; Psoas Abscess; Ultrasonography

Pseudomyxoma peritonei (PMP) is a rare malignancy, and there is insufficient evidence about systemic chemotherapy for this disease.. We retrospectively evaluated the efficacy and safety of a chemotherapeutic regimen with 5-fluorouracil and oxaliplatin (modified FOLFOX6, mFOLFOX6) for patients with unresectable pseudomyxoma peritonei. Patients who received the therapy between April 2000 and February 2019 at the Department of Medical Oncology, Tohoku University Hospital, were enrolled in this study.. Eight patients were treated with mFOLFOX6. The sites of primary tumor were appendix in six patients, ovary in a patient, and urachus in a patient. Six patients received surgery. Seven patients had histologically high-grade PMP, and one patient had low-grade PMP. The median follow-up duration was 27.2 months. All the patients had non-measurable regions as the targets of tumor response. Non-complete response or non-progressive disease was observed in seven patients, with a disease control rate of 87.5%. The median progression-free survival and overall survival were 13.0 months and 27.9 months, respectively. An obvious reduction in the symptoms was observed in two patients. Five patients experienced decline in the serum tumor markers, CEA or CA19-9. The grade 3/4 toxicity that was observed was grade 4 neutropenia in one patient and grade 3 neutropenia in two patients.. mFOLFOX6 might be an effective and tolerable treatment option for patients with unresectable PMP. To our knowledge, this is the first case series of mFOLFOX6 in patients with unresectable PMP and the first case series of systemic chemotherapy for Asian patients with unresectable PMP.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; CA-19-9 Antigen; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Progression-Free Survival; Pseudomyxoma Peritonei; Retrospective Studies; Treatment Outcome

Pseudomyxoma peritonei is a disease that results from a perforated mucinous neoplasm of the appendix so that mucinous ascites and mucin-producing tumor cells are widely disseminated in a characteristic pattern throughout the abdomen and pelvis. The intraabdominal mucus can accumulate in the inguinal canal and by physical examination be indistinguishable from the usual inguinal hernia.. A database of patients with pseudomyxoma peritonei was used to identify patients who had an inguinal hernia prior to or at the time of cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC). At the time of CRS, care was taken in all patients to remove the peritoneal lining of the inguinal canal. Patients who had the inguinal hernia repaired prior to definitive treatment with CRS and HIPEC had all tissue and mesh associated with prior herniorrhaphy resected.. In 178 pseudomyxoma peritonei patients, 17 had a new onset or previously repaired inguinal hernia that required extraction of mucus and mucinous tumor from the hernia site. No repair of the open inguinal canal was attempted at the time of CRS. No recurrent inguinal hernias were recorded and no patients required an inguinal incision at a later time to resect progressive disease within the inguinal canal.. Inguinal hernias caused by mucinous ascites and tumor were definitively treated by cytoreductive surgery plus HIPEC. Extraction of tumor and peritoneum from the inguinal canal facilitates fibrous closure of the hernia defect so that hernia recurrence was not observed.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Ascites; Cytoreduction Surgical Procedures; Doxorubicin; Female; Fluorouracil; Hernia, Inguinal; Humans; Hyperthermia, Induced; Infusions, Parenteral; Inguinal Canal; Leucovorin; Male; Middle Aged; Mitomycin; Mucus; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Retrospective Studies; Tomography, X-Ray Computed

Currently, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are accepted treatments for surgically resectable appendiceal epithelial neoplasms. However, for nonsurgical candidates, systemic treatment may be considered. The purpose of this analysis was to determine the benefit of biologic therapy (anti-vascular endothelial growth factor and anti-epidermal growth factor receptor) in addition to systemic chemotherapy in this select patient population.. The MD Anderson Cancer Center tumor registry was retrospectively reviewed for systemic treatment-naive appendiceal epithelial neoplasm patients registered between January 2000 to July 2007 for prior cytoreductive surgery and hyperthermic intraperitoneal chemotherapy status, histologic grade, signet ring pathology, systemic chemotherapy, biologic therapy, tumor markers (carcinoembryonic antigen, carbohydrate antigen [CA] 125, and/or CA19-9), progression-free survival (PFS), overall survival (OS), and disease control rate. Kaplan-Meier method, log-rank, and Cox proportional hazard regression models were used for statistical analysis.. A total of 353 patients were identified; 130 patients met the inclusion criteria. Fifty-nine patients received biologic therapy. The use of the anti-vascular endothelial growth factor (VEGF) agent bevacizumab improved both OS (42 months vs. 76 months, hazard ratio 0.49 [95 % confidence interval 0.25-0.94] P = 0.03) and PFS (4 months vs. 9 months, hazard ratio 0.69 [95 % confidence interval 0.47-0.995], P = 0.047) for all histologic subtypes. Moderately differentiated tumors had an improved PFS relative to well-differentiated tumors, 9 months versus 3 months (P = 0.05).. Bevacizumab in combination with chemotherapy appears to play a role in surgically unresectable appendiceal epithelial neoplasm patients, with an improvement in PFS and OS. Anti-VEGF agents should be strongly considered in the management of patients with higher-grade appendiceal epithelial neoplasms who are suboptimal candidates for surgical resection.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Bevacizumab; CA-19-9 Antigen; Camptothecin; Capecitabine; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Cetuximab; Cisplatin; Cytoreduction Surgical Procedures; Disease-Free Survival; ErbB Receptors; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Grading; Organoplatinum Compounds; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Retrospective Studies; Survival Rate; Tumor Burden; Vascular Endothelial Growth Factor A

The standard treatment of peritoneal pseudomyxoma is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma. The aim of our study was to assess the activity of chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX-4 regimen) in terms of response rate in this subset of patients.. Patients were included in a single-center, observational study and treated with FOLFOX-4 administered every 2 weeks for up to 12 cycles or until progressive disease or unacceptable toxicity.. Twenty consecutive patients were reviewed from July 2011 to September 2013. Only partial responses were observed, with an objective response rate of 20%. Median progression-free survival and overall survival were 8 months and 26 months, respectively. Two patients were able to undergo laparotomy with complete cytoreduction and HIPEC in one case. Safety data for FOLFOX-4 were consistent with the literature. By means of a mutant enriched polymerase chain reaction, KRAS mutation was found in 16 of 19 cases (84%), and MGMT promoter methylation was found in 8 (42%, all KRAS mutant).. FOLFOX-4 chemotherapy is tolerable and active in patients with peritoneal pseudomyxoma when disease is deemed unresectable or relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers, such as KRAS for resistance to anti-epidermal growth factor receptor monoclonal antibodies and MGMT for response to temozolomide, is a priority for the development of evidence-based treatment strategies for peritoneal pseudomyxoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Pseudomyxoma Peritonei; ras Proteins; Treatment Outcome; Tumor Suppressor Proteins

Delayed repeated intraperitoneal chemotherapy after cytoreductive surgery for carcinomatosis may be an alternative to intraoperative hyperthermic infusion.. The aim of this study was to evaluate the safety and feasibility of delayed repeated intraperitoneal chemotherapy after cytoreduction of colorectal and appendiceal carcinomatosis and pseudomyxoma peritonei.. This study constitutes a retrospective case series.. This study was conducted at a single institution.. A total of 31 patients with peritoneal carcinomatosis (23) and pseudomyxoma peritonei (8) were included.. Cytoreduction was followed by placement of an adhesion barrier and intraperitoneal catheters. Peritoneal scintigraphy preceded biweekly intraperitoneal 5-fluorouracil and systemic combination chemotherapy with leucovorin, fluorouracil, and oxaliplatin (FOLFOX).. The primary outcomes measured are safety, feasibility, and short-term survival.. Cytoreduction to a score of 0 to 1 was possible in 25 patients (80%). Complications occurred in 16 patients (51.6%) and were confined to grades I to III. There were no deaths, and no digestive fistulae occurred. Port malfunction or complication resulted in removal in 5 patients (16.1%). Intraperitoneal chemotherapy was possible in 83.8% of patients; 55% completed the full course. Peritoneal scintigraphy demonstrated free diffusion of tracer in 18 patients (58%), 4 (12.9%) had diffusion in each gutter with limited communication, 5 (16.1%) had limited diffusion around each catheter without communication, and 2 (6.5%) had no diffusion on scintigraphy. Overall survival for peritoneal carcinomatosis was 44.5% at 3 years (95% CI = 23%-65%).. The nonrandomized nature of this study and the early experience are limitations.. Delayed repeated intraperitoneal and systemic chemotherapy after cytoreduction is feasible and has acceptable morbidity rates. Delayed intraperitoneal chemotherapy is possible in 83% of patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Colorectal Neoplasms; Combined Modality Therapy; Disease Progression; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Patient Safety; Pseudomyxoma Peritonei; Radionuclide Imaging; Retrospective Studies; Survival Rate; Time Factors

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cecal Neoplasms; Cetuximab; Colectomy; Combined Modality Therapy; Diagnosis, Differential; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Lung Neoplasms; Male; Neoplasm Staging; Organoplatinum Compounds; Palliative Care; Peritoneal Neoplasms; Positron-Emission Tomography; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Pseudomyxoma Peritonei; ras Proteins; Whole Body Imaging

Effective systemic therapy for advanced pseudomyxoma peritonei (PMP) is the focus of investigation. We describe a case of PMP arising from an adenoma of the appendix in a 58-year-old man. First, the patient underwent explorative laparotomy with ileocoecal resection, but without possibility of major tumor debulking due to adhesive gross tumor masses. Subsequently, six cycles of Folfox IV chemotherapy were administered, without response, but with severe side effects. Upon progressive disease, a combination of bevacizumab and capecitabine led to a long term stabilization of disease and obvious improvement of performance status. Our case suggests that modulation of tumor microenvironment and angiogenesis by bevacizumab, potentially augmented by moochemotherapy, may be beneficial in borderline tumors such as PMP.

Topics: Adenoma, Villous; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Bevacizumab; Capecitabine; Combined Modality Therapy; Deoxycytidine; Disease Progression; Fluorouracil; Hernia, Inguinal; Humans; Ileocecal Valve; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Treatment Outcome

Pseudomyxoma peritonei (PMP) is a rare condition characterized by mucinous tumors, disseminated intra-peritoneal implants, and mucinous ascites. So far its diagnosis remains challenging to most clinicians.. A 55-year-old male patient had suffered from acute onset of abdominal pain and abdominal distension for one day prior to his admission. Physical examination revealed tenderness over the right lower quadrant of the abdomen without diffuse muscle guarding. A large amount of ascites was identified by abdominal computed tomography (CT) scan. Paracentesis showed the appearance of sticky mucinous ascites. He underwent laparotomy under the impression of pseudomyxoma peritonei. There was a lot of mucinous ascites, one appendiceal tumor and multiple peritoneal implants disseminated from the subphrenic space to the recto-vesicle pouch. Pseudomyxoma Peritonei caused by mucinous adenocarcinoma of appendiceal origin, was confirmed by histopathology. We performed an excision of the appendiceal tumor combined with copious irrigation and debridement. After the operation, he received 10 cycles of systemic chemotherapy with FOLFOX4 regimen, without specific morbidity. Follow-up of abdominal CT and colonoscopy at post-operative 17 months showed excellent response without evidence of local recurrence or distal metastasis. He made an uneventful recovery (up to the present) for 21 months after the operation.. This case report emphasizes the possible new role of systemic chemotherapy in the treatment of patients with this rare clinical syndrome.

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Chemotherapy, Adjuvant; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Tomography, X-Ray Computed

The modern treatment of pseudomyxoma peritonei is cytoreductive surgery plus intraperitoneal chemotherapy resulting in a survival of up to 70 percent after 20 years. The goal of this study was to investigate the impact on quality of life of this very aggressive treatment, which has not been done before.. Twenty-three prospective patients underwent cytoreductive surgery and early postoperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Patients were followed in clinic 3, 6, 12, 18, and 24 months after surgery and had CT scan of the abdomen every 6 months. Quality of life was prospectively assessed with the generic quality of life instrument Short Form-36 Questionnaire, together with the two symptom-specific instruments--European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and Colorectal Cancer Module 38--before surgery and at every postoperative visit.. Complete cytoreduction was achieved in 21 patients. No patients died within 30 days. Seventy percent of patients had one or more complications during or after surgery, but all had recovered. Fourteen percent had an asymptomatic recurrence detected within two years. The impact on quality of life of the disease and of its treatment was very modest despite the high morbidity after the treatment. There was a significant decrease in the scores on the Short Form-36 Questionnaire scales of physical dimension and role physical three months after surgery, only returning to normal after another three months. The other scores corresponded to the scores in a normal population.. Cytoreductive surgery plus early postoperative intraperitoneal chemotherapy is an extensive treatment with a high morbidity but with relatively little impact on quality of life in patients with pseudomyxoma peritonei.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Peritoneal Neoplasms; Prospective Studies; Pseudomyxoma Peritonei; Quality of Life; Statistics, Nonparametric; Survival Rate; Treatment Outcome

We report a case of pseudomyxoma peritonei caused by carcinoma of the appendix, which was successfully treated with multidisciplinary treatment including modified FOLFOX6 regimen. A 45-year-old man was diagnosed as having peritoneal dissemination associated with cancer of the cecum or appendix. Seven cycles of mFOLFOX6 treatment resulted in a marked decrease in ascites and serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9. At laparotomy, a diagnosis of pseudomyxoma peritonei caused by cancer of the appendix was made. Intraperitoneal lavarge with 10,000 mL 5% glucose was performed after right hemicolectomy, omentectomy and removed of mucinous peritoneal nodules. Intraperitoneal chemotherapy comprised of 3000 mL low molecule dextran and 80 mg cisplatin was added on postoperative days 7 and 14. Modified FOLFOX6 regimen was started again two months postoperatively and reached 28 cycles. The patient does not show any sign of recurrence 12 months postoperatively.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Colonoscopy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Pseudomyxoma Peritonei; Tomography, X-Ray Computed

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Peritoneal Neoplasms; Peritoneum; Pseudomyxoma Peritonei

Pseudomyxoma peritonei remains a fatal disease. However, extensive surgical cytoreduction combined with intraoperative heated intraperitoneal chemotherapy (HIPEC) has recently emerged as a new treatment modality, which might improve survival.. Patients underwent treatment if the tumour appeared to be technically resectable on preoperative abdominal computed tomography and there were no distant metastases. After aggressive surgical cytoreduction, HIPEC with the administration of mitomycin C was performed for 90 min. Depending on histological grading, patients received adjuvant 5-fluorouracil and leucovorin therapy.. Forty-six patients were treated. Optimal surgical cytoreduction was obtained in 40 patients. Postoperative surgical complications occurred in 18 patients. Four patients died as a direct result of the treatment. Bone marrow suppression due to mitomycin C toxicity occurred in 22 patients. There was no other major toxicity related to the HIPEC procedure. After a median follow-up of 12 months, 40 patients are alive, eight of whom have proven recurrence. The actuarial survival rate (Kaplan-Meier) at 3 years was 81 per cent.. These results confirm that extensive surgery combined with HIPEC is feasible in patients with pseudomyxoma peritonei and that improved long-term survival might be achieved.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Infusions, Intravenous; Injections, Intravenous; Length of Stay; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Postoperative Complications; Pseudomyxoma Peritonei; Reoperation; Treatment Outcome

In a retrospective study, the potential and limitations of surgical therapy of pseudomyxoma peritonei were studied in seven patients. In all patients the pseudomyxoma had originated from the appendix. All patients were primarily treated by surgery. An R0 resection at the first operation was possible in only one patient with a benign pseudomyxoma, while significant tumor debulking with improved symptoms was achieved in all other patients. If the tumor recurred relaparotomy was performed to obtain tumor reduction. The perioperative morbidity even after multiple relaparotomies was low. The survival rates ranged between 2 and 20 years with chemotherapy (5-fluorouracil) which was of particular prognostic benefit in patients with malignant pseudomyxoma peritonei. Surgical therapy is the treatment of choice in pseudomyxoma peritonei, although an R0 resection is hardly feasible. Due to the low morbidity, relaparotomy in cases of tumor recurrence always appears to be indicated. In comparison to other gastrointestinal malignancies, the survival rates in pseudomyxoma peritonei, sometimes treated with additive chemotherapy, are superior.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Humans; Infusions, Parenteral; Interferons; Leucovorin; Male; Methotrexate; Middle Aged; Peritoneum; Pseudomyxoma Peritonei; Retrospective Studies