Cancer Research and Treatment

Combined Cytoreductive Surgery and Early Postoperative Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Gastric Cancer: Kwang Il Ha, Ho Yoon Bang, Jong Inn Lee; Cancer Res Treat. 2003;35(6):507-513. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.507

Abstract PDF: PURPOSE
Peritoneal seeding is the most common type of metastasis or recurrence and one of the poor prognostic factors in gastric cancer. Moreover, there are as yet no effective treatment modalities available. Recently some research groups suggested the benefit of combined cytoreductive surgery and intraperitoneal chemotherapy, but the related experiments remain in the trial stage. Therefore, we assessed the safety and evaluated the efficacy of combined cytoreductive surgery and early postoperative intraperitoneal chemotherapy (EPIC) in gastric cancer patients with peritoneal carcinomatosis of gastric cancer.
MATERIALS AND METHODS
From Nov. 1997 to May. 2002, eighteen cases of combined cytoreduction and EPIC were performed in the Korea Cancer Center Hospital due to gastric cancer with peritoneal carcinomatosis. The control group consisted of 33 patients who had no resection without EPIC during the same periods. After combined cytoreductive surgery and EPIC, all patients received systemic chemotheraphy with the exception of 2 patients who could not tolerate the treatment. We retrospectively investigated the clinicopathologic features and analyzed the factors affecting the prognosis. Median follow-up period was 11.9 months (range 0.5~61 months). Statistical analysis was performed by SPSS 11.0 for Windows. A P-value less than 0.05 was considered as statistically significant. RESULTS: There was one case of the treatment-related mortality (5.5%) and seven cases of treatment-related complications (38%) in the combined cytoreductive surgery and intraperitoneal chemotherapy group. One-, 3- and 5-year survival rates of cytoreductive surgery plus EPIC were 57.6%, 25.9% and 13.0%, respectively, and those of the control group were 18.2%, 3% and 0%, respectively. Survival of the combined cytoreductive surgery plus EPIC group was better than that of the control group (p=0.0026). In multivariate analysis of prognostic factors affecting the survival, combined cytoreductive surgery plus EPIC (p=0.02) and systemic chemotherapy (p=0.019) were independent prognostic factors. CONCLUSION: Although a small number of cases were included in this study, combined cytoreductive surgery plus EPIC showed survival benefit and retained a comparable complication rate compared with the control group.

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Phase I and Pharmacokinetic Study of Intraoperative Intraperitoneal Heptaplatin in Patients with Surgically Resected Advanced Gastric Cancer: Wansik Yu, Ho Young Chung, So Hyang Park, Yong Baik Cho, Yang Soo Lim; Cancer Res Treat. 2003;35(1):25-29. Published online February 28, 2003; DOI: https://doi.org/10.4143/crt.2003.35.1.25

Abstract PDF: PURPOSE
Heptaplatin, a new platinum analog, has favorable toxicity profiles and antitumor activity, comparable to those of cisplatin, in the treatment of gastric cancer. This study was designed to define the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and pharmacokinetics of heptaplatin administered by an intraperitoneal route in patients with resected advanced gastric cancer. MATERIALS AND METHODS: Seventeen patients with resected advanced gastric cancer were entered onto the study. After completion of a curative resection and an astomosis, heptaplatin was administered intraperiton eally in one liter of 5% dextrose solution. The starting heptaplatin dose was 400 mg/m2 of the body surface area, and was escalated in 200 mg/m2 increments, to cohorts of three patients. A pharmacokinetic analysis was carried out to determine the total and ultrafiltratable platinum concentrations in the plasma, peritoneal fluid, and urine. RESULTS: Patients were unable to tolerate a 1, 000 mg/m2 dose level, and at 800 mg/m2, reVersible Grade III toxic ities, including elevated creatinine, proteinuria, hypon- atremia, abdominal pain, and intraabdominal bleeding were noted. No significant toxicity was noted up to a 600 mg/m2 dose level. The ratio of the peak peritoneal to peak plasma drug concentrations were 19.4, 16.6 and 22.8 at doses of 400 mg/m2, 600 mg/m2 and 800 mg/m2, respectively. The pharmacological advantage, expressed as the peritoneal to plasma AUC ratio ranged from 4.3 to 7.0. CONCLUSION: Heptaplatin can be delivered by an intra peritoneal route, with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure. The MTD of intraperitoneal heptaplatin was 800 mg/m2. The major DLTs were nephrotoxicity and intraabdominal bleeding. The recommended starting dose for a subsequent study would be 600 mg/m2.

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Intraperitoneal Administration of 5 - Fluorouracil in Advanced Gastrointestinal Cancer: Kyu Joo Park, Jae Gahb Park, Kuk Jin Choe, Jin Pok Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1990;22(3):567-579.

Abstract PDF: In gastrointestinal malignancies such as cancer of stomach, large bowel and ovary, peritoneal involvement with metastatic tumor is a common finding at the time of initial operation or following initial curative resection of the tumor. Intraperitoneal administration of chemotherapeutic agents offers an opportunity to deliver high concentration of drug to local intraperitoneal surfaces and also to liver as most of drug administered intraperitoneally is cleared via the portal vein. Thus, Intraperitoneal (IP) chemotherapy should permit more effective treatment of peritoneal surfaces and liver while reducing systemic toxicities of the chemotherapeutic 'agents. In an effort to evaluate the efficacy and safety of IP chemotheray, we have treated 6 advanced stomach cancer patients (including 2 stage IV stomach cancer patients) and I colon cancer patient who had undergone surgery at Department of Surgery, Seoul National University HapitaL Each cycle of treatment consisted of daily intraperitoneal administration of 5-fluorouracil through Tenckhoff peritoneal dialysis catheter for 5 days in every four weeks. Initial dose of IP 5-FU was 20 ml/kg body wt, with dosage increment each cycle until toxicity was experienced by the patient. The following results were obtained: 1) Mean daily dose of 5-FU administered was 1500 mg, and maximal daily dose administered to each patient ranged from 1100 to 2030 mg (21 to 30 mg/kg body wt.) with a mean maximal dose of 1567 mg (28mg/kg body wt.) 2) Most common toxicities related to 5-FU were nausea, vomiting, and diarrhea which were self -limited. Hepatotoxicity appeared in 3 patient, but only in one patient was it severe enough to discontinue therapy. Hematotoxicity appeared in 1 patient as manifested by leukopenia (WBC< 4000/ mm(3)) but was able to continue therapy after dosage reduction. 3) Complications related to Tenckhoff catheter were catheter obstruction, leakage of fluid around the catheter and intestinal obstruction which occurred in one patient respectively. There was no incidence of skin infectian or bacterial peritonitis. 4) Common discomfort after IP administration of 5-FU was abdominal fullness and self-limited ahdominal pain, but there was no inicidence of chemical peritonitis. 5) Three advanced stomach cancer patients died at 4 months, S months and 12months postoperatively, but one patient who had peritoneal seeding at the time of operation remained disease free for 32 months after 12 cycles of 5-FU IP therapy. Remaining 3 patients are free of recurrence at 20 months postoperatively. IP chemotherapy is a relatively safe method of administrating a large dose of 5-FU to intraperitoneal space as well as to the hepatic parenchyme. Further clinical testing of this route of administration is clearly warranted both for prevention and treatment of peritoneal and hepatic metastasis of gastrointestinal cancers.

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Four Cases of Primary Urachal Adenocarcinoma: Don Haeng Lee, Hyun Cheol Chung, Young Jin Kim, Sin Ki Ahn, Young Ho Kim, Dong Lip Kim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Young Tae Lee, Eun Kyung Han, Hyun Joo Chung, Gui Eon Kim, Byung Soo; J Korean Cancer Assoc. 1990;22(3):579-587.

Abstract PDF: The primary adenocarcinoma of bladder is a rare cancer and it was known that the prognasis is poor. The primary adenocarcinoma of bladder is divided by its embriological orign: I) nonurachal carcinoma derived from transformation of bladder epithelium, 2) urachal carcinoma arising from urachal remnant. This report represent four cases of primary urachal adenocarcinoma at Yonsei University Medical College from 1971 to 1989. The commonest sign is a painless hematuria. The specific site of origin is evaluated by measns of cystocopy, ultrasonography and computerized tomography. The choice of treatment is wide surgical resection and the role of chemotheraphy and radiotheraphy is still controversial. Our first two cases were treated only conservatively in advanced stages. The third cases was treated by curative resection and postoperative adjuvant chemotherapy. But 10 months later, intraabdominal carcinomatosis was developed. The fouth case showed metastatic lesions in both lung fields at the time of diagnosie. So we started chemotherapy of FAM regimen and a partill response was noticed after 3 cycles of chemotherapy. But after additional 3 cycles, the metastatic resions were aggrevated.

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Three Cases of Endodermal Sinus Tumor in Pediatric Age: Sang Wook Choi, Mi Jeong Lee, Kyung Ja Cho, Ja June Jang; J Korean Cancer Assoc. 1990;22(3):587-595.

Abstract PDF: We experienced three cases of Enclodermal sinus tumor (EST) during 9 months of period developed at intestine ovary and sacrococcyx. EST is the most common Gerrn cell tumor in pediatric age. The sacror occygeal area is the major site of involvement in the newborn and infant; in older children, the ovary is the chief location. Like most Germ cell tumor, EST is very sensitive to Chemotherapy and thc long term survior have been reported recently with the regimen containing CDDP (cisplatinum).

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Treatment of Olfactory Neuroblastoma with Combination Chemotherapy and radiation Therapy: Jong Youl Jin, Choon Snag Bang, Hoon Kyo Kim, Kyung Shik Lee, Dong Jip Kim, Min Sik Kim, Seung Ho Cho, Byung Do Suh, Sei Chul Yoon, Kyu Ho Choi; J Korean Cancer Assoc. 1990;22(3):595-600.

Abstract PDF: Olfactory neuroblastoma (esthesioneuroblastoma) is very rare nasal tumor, which develops in the olfactory mucosa. Since the first description by Berger et al in 1924, about 200 cases have been reported in the literature. And there have been 3 reports since 1964 in Korea. All the reported cases in Korea were treated with surgical resection and or radiotherapy. The authors have experienced complete remission with combination chemotherapy and radiation therapy in a patient with olfactory neuroblastoma. A 55-year-old male presented with advanced unresectable olfactory neurobIastoma (stage C) and he was treated with combination chemotherapy (cisplatin, adriamycin, VM-26, cycloposphamide) every 3-4 weeks for 5 times followed by radition therapy (64BO cGy/36 fractions/9 weeks), which resulted in complete remission. The patient had been free of disease and asymptomatic for 8 months after treatment. Rescently left facial nerve palsy developed, of which etiology due to recurrence or treatment related fibrosis is unclear. Now, the authors are on study the etiology of left facial nerve palsy.

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