GYNAECOLOGY

GYNAECOLOGY

Intraperitoneal Chemotherapy for Advanced Ovarian and Peritoneal Cancers in Patients Following Interval Debulking Surgery or Primary Cytoreductive Surgery: Tom Baker Cancer Centre Experience From 2006 to 2009
Gregory Nelson, MD, PhD, FRCSC, Carlos Aspe Lucero, MD, Pamela Chu, MD, FRCSC, Jill Nation, MD, FRCSC, Prafull Ghatage, MBBS, FRCSC
Division of Gynecologic Oncology, Tom Baker Cancer Centre, Calgary AB

Abstract
Objective: To describe our experience with cisplatin- and paclitaxel-based IP chemotherapy in patients treated initially with either neoadjuvant chemotherapy and interval debulking surgery (IDS) or primary cytoreductive surgery (PCRS). Methods: We performed a retrospective review of the records of 67 patients (38 IDS, 29 PCRS) enrolled in the intraperitoneal (IP) chemotherapy program at the Tom Baker Cancer Centre between 2006 and 2009. Information pertaining to patient demographics, IP chemotherapy toxicity, and catheter complications was extracted, and the median time to recurrence was calculated. Results: Most patients in the study were aged 50 to 70 years and had a diagnosis of stage III serous ovarian cancer. Overall, 295/393 IP cycles (75%) were successfully administered. The proportion of patients completing six cycles of chemotherapy in the IDS and PCRS groups was 53% and 59%, respectively. Frequent (> 25%) Grade 1 to 2 chemotherapy toxicities included fatigue, peripheral neuropathy, and nausea. Catheter complications were observed in 34% of patients (23/67). The recurrence rates for patients completing four or more cycles of IP chemotherapy in the IDS and PCRS groups were 58% and 35%, respectively, with the median time to recurrence approximately one year. Conclusion: Although IP chemotherapy is well tolerated in both IDS and PCRS patients, the median time to recurrence is shorter than expected.

Rsum
Objectif : Dcrire notre exprience en ce qui concerne ladministration dune chimiothrapie intrapritonale (IP) au cisplatine et au paclitaxel des patientes initialement traites au moyen dune chimiothrapie noadjuvante et dune chirurgie de rduction tumorale dintervalle (CRTI) ou dune chirurgie de rduction tumorale primaire (CRTP). Mthodes : Nous avons men une analyse rtrospective des dossiers de 67 patientes (38 CRTI, 29 CRTP) ayant particip au programme de chimiothrapie IP du Tom Baker Cancer Centre entre 2006 et 2009. Les donnes sur les caractristiques dmographiques des patientes, la toxicit de la chimiothrapie IP et les complications associes au cathter ont t extraites et le dlai mdian jusqu la rcurrence a t calcul. Rsultats : La plupart des participantes ltude taient ges de 50 70 ans et prsentaient un diagnostic de cancer sreux de lovaire de stade III. En tout, 295/393 cycles IP (75 %) ont t administrs avec succs. La proportion de patientes se soumettant six cycles de chimiothrapie au sein des groupes CRTI et CRTP tait de 53 % et de 59 %, respectivement. Parmi les toxicits chimiothrapeutiques de stade 1 a 2 frquentes (> 25 %), on trouvait la fatigue, la neuropathie priphrique et la nause. Des complications associes au cathter ont t constates chez 34 % des patientes (23/67). Les taux de rcurrence chez les patientes se soumettant quatre cycles de chimiothrapie IP ou plus au sein des groupes CRTI et CRTP taient de 58 % et de 35 %, respectivement, le dlai mdian jusqu la rcurrence tant denviron un an. Conclusion : Bien que la chimiothrapie IP soit bien tolre tant chez les patientes soumises une CRTI que chez celles qui sont soumises une CRTP, le dlai mdian jusqu la rcurrence est plus court que prvu. J Obstet Gynaecol Can 2010;32(3):263269

Key Words: Ovarian cancer, intraperitoneal chemotherapy, interval debulking surgery, recurrence Competing Interests: None declared. Received on September 9, 2009 Accepted on October 18, 2009

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INTRODUCTION

n January 2006 the United States NCI issued a clinical alert on the use of IP chemotherapy as the preferred method of treatment in women with optimally debulked (< 1 cm) stage III epithelial ovarian cancer.1 This recommendation was based largely on the results of three randomized clinical trials,24 most notably the GOG trial 172, which showed a nearly 16-month overall median survival advantage for patients treated with IP cisplatin/paclitaxel versus IV chemotherapy alone. Despite the survival advantage, patients receiving IP chemotherapy during this trial reported significantly worse quality of life measures as a result of increased toxicity and catheter complications. Because of this, instituting IP chemotherapy programs across Canada and the United States has been met with some resistance. This was demonstrated recently in a US survey of oncologists regarding their use of IP chemotherapy in women with ovarian cancer, which showed that 23% of respondents did not provide IP chemotherapy.5 The main reasons reported for favouring traditional IV chemotherapy over the IP approach were the lower toxicity of IV and the lack of facilities to give an IP infusion. The survey also highlighted the vast differences in IP chemotherapy regimens currently employed, with respect to chemotherapy dose, outpatient versus inpatient administration, and timing of catheter insertion. Recent evidence also indicates that the use of IP chemotherapy is not restricted to patients treated with PCRS, as was the standard in the landmark clinical trials.24 Tiersten et al.,6 in the first study of its kind, reported outcomes for 26 patients treated with neoadjuvant chemotherapy and IDS who were subsequently treated with carboplatin-based IP chemotherapy. The PFS and OS were 29 and 34 months, respectively. These results have become particularly relevant, given the preliminary findings of the

EORTC-GCG/NCIC-CTG randomized trial comparing primary debulking surgery with neoadjuvant chemotherapy in stage IIIIV ovarian cancer.7 While the OS and PFS were equivalent in both groups, postoperative mortality, sepsis, and hemorrhage were significantly lower in the neoadjuvant group. Based on the results of this study, there may be a shift towards neoadjuvant chemotherapy as the preferred treatment. In accordance with the NCI clinical alert, an organized IP chemotherapy program for advanced optimally debulked ovarian, peritoneal, and fallopian tube cancers was instituted at the TBCC in early 2006. Both PCRS and IDS patients were enrolled in the program. The objective of this study was to document our experience at TBCC with cisplatin- and paclitaxel-based IP chemotherapy in both PCRS and IDS patients, and thus provide further insight into management of this disease.
MATERIALS AND METHODS

The TBCC is a tertiary level facility which provides comprehensive cancer care for all patients from southern Alberta and draws referrals from both western Saskatchewan and eastern British Columbia. Gynaecologic oncology support (radical surgery, chemotherapy) is currently provided by three gynaecologic oncologists (P.C., P.G., and J.N.). An electronic medical chart (Aria Oncology Information System, Varian Medical Systems, Inc., Palo Alto, CA) is used to record all patient information at TBCC from initial consultation to post-treatment follow-up. Using this system, all patients enrolled in the IP chemotherapy program from 2006 (program inception) to May 2009 were identified. Patients eligible for review were required to have completed chemotherapy. Sixty-seven patients were identified and chart review was undertaken. The following data were extracted from each chart: age at diagnosis, stage and histologic type of cancer, adequacy of debulking, whether radical procedures were performed (e.g., bowel resection, splenectomy, diaphragm stripping), and location and timing of IP catheter insertion. Toxicity of chemotherapy and catheter-specific complications were recorded from clinic notes and nurse memoranda between visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.8 The number of IP chemotherapy cycles completed was recorded for each patient, as were reasons for premature discontinuation of IP chemotherapy. Thirty-eight of the 67 patients (IDS group) were treated with neoadjuvant chemotherapy (carboplatin/paclitaxel IV) prior to optimal IDS and subsequent IP chemotherapy. One or more of the following factors contributed to the use

ABBREVIATIONS CTG Clinical Trials Group EORTC European Organisation for Research and Treatment of Cancer GCG GOG IDS IP NCI NCIC OS PCRS PFS TBCC Gynaecological Cancer Group Gynecologic Oncology Group interval debulking surgery intraperitoneal (United States) National Cancer Institute National Cancer Institute of Canada overall survival primary cytoreductive surgery progression-free survival Tom Baker Cancer Centre

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Table 1. Outpatient IP chemotherapy regimen

Day 1 Ranitidine 50 mg IV, diphenhydramine 50 mg IV, dexamethasone 20 mg IV, and granisetron 1 mg IV pre-chemotherapy Normal saline (NS) 1000 mL IV pre-hydration over 2 hours Paclitaxel 135 mg/m2 IV NS 250 mL IP infusion pre-cisplatin (by gravity) Cisplatin 75 mg/m2 in 1000 mL NS IP infusion (by gravity) NS 500 mL IV post-hydration with magnesium sulphate 4 g added Furosemide 40 mg PO at completion of day 1 chemotherapy Day 8 Ranitidine, diphenhydramine, dexamethasone, granisetron pre-chemotherapy as above NS 250 mL IP infusion pre-paclitaxel (by gravity) Paclitaxel 60 mg/m2 in 1000 mL NS IP infusion (by gravity)

of neoadjuvant chemotherapy in patients without prior suboptimal debulking surgery (n = 31): grossly elevated CA-125 level (median 988 kU/L, range 20013800 kU/L), peritoneal carcinomatosis (25/31, 81%), splenic or liver lesions or both (12/31, 39%), pleural effusion (10/31, 32%), and diaphragmatic disease (1/31, 3%). Cytology was confirmed positive for metastatic adenocarcinoma in 90% (28/31) of IDS patients. In the IDS group, the number of neoadjuvant chemotherapy cycles given, the extent of disease from pre-treatment CT scans, and pre-treatment CA-125 levels were recorded. The remaining 29 patients (PCRS group) had PCRS followed by IP chemotherapy. IP chemotherapy was administered in all patients through the use of a titanium port attached to a 9.6 Fr single lumen catheter (Bard Access Systems, Salt Lake City, UT). Ports were inserted primarily at the time of surgery in varying locations depending on surgeon preference and flushed with 10 mL of heparinized saline (100 USP U/mL) as per the manufacturers protocol. IP chemotherapy was given in an outpatient setting on Days 1 and 8 of a 21-day cycle (Table 1) with an intended treatment duration of six cycles. Cisplatin 75 mg/m2 was given by IP infusion together with paclitaxel 135 mg/m2 IV on day 1 followed by paclitaxel 60 mg/m2 IP alone on Day 8. Standard anti-emetics were given, as were medications to prevent anaphylaxis. The results of a complete blood count, serum electrolytes, serum magnesium, serum creatinine, and liver panel were reviewed prior to each cycle, and patients were assessed in the clinic by a gynaecologic oncologist or resident/fellow prior to every other cycle. Filgrastim was used if there was persistent neutropenia causing treatment delay. All patients who discontinued IP chemotherapy prematurely were switched to carboplatin/ paclitaxel IV to complete a total of six treatment cycles.

Charts were examined for evidence of recurrent disease or death. Median time to recurrence was chosen as a surrogate for PFS and was defined as the duration from start of postoperative chemotherapy to radiologic evidence of recurrent disease. Approval from the University of Calgary Conjoint Health Research Ethics Board was obtained prior to commencement of the study.
RESULTS

The patient and disease characteristics for both the IDS and PCRS groups are listed in Table 2. In the IDS group (n = 38), the median age at diagnosis was 61 (range 30 to 75). The majority of patients had FIGO stage III (82%), serous (87%) ovarian carcinoma (74%). Ten patients (26%) had primary peritoneal carcinoma. Most IDS patients (34/38, 89%) had three cycles of neoadjuvant chemotherapy (3 had 4 cycles, 1 had 2). Seven of 38 patients had suboptimal debulking at initial surgery (3/7 were referred from general gynaecologists). In the PCRS group (n = 29), the median age at diagnosis was 56 (range 3575). Similar to the IDS group, most patients in the PCRS group had FIGO stage III (83%), serous (69%) ovarian carcinoma (97%). Only one patient (3%) had primary peritoneal carcinoma. There were no patients in either group who had fallopian tube carcinoma. In both groups, there were only a few patients who had endometrioid, clear cell, and other rare (undifferentiated, mixed, transitional) histologies. In both groups, there were similar numbers of patients in whom microscopic optimal debulking was achieved (IDS 26%, PCRS 21%). Bowel resection was performed in four patients (colon resection in three, small bowel resection in one) in the IDS group (11%). No bowel resections were
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performed in the PCRS group. Splenectomy or diaphragm stripping was required in only a select few patients. There was no radiologic evidence of peritoneal carcinomatosis or upper abdominal disease in any of the PCRS patients. The degree of optimal debulking (microscopic vs. < 1 cm) was similar in both groups. In all patients, the majority of IP catheters were placed in the left upper quadrant at the time of surgery. Only one patient (in the PCRS group) had the catheter placed postoperatively by mini-laparotomy. There were no patients in whom catheter insertion was delayed due to bowel resection. The number of cycles of IP chemotherapy completed is shown in Table 3 (1 cycle = completion of both Day 1 and Day 8 chemotherapy as detailed in Table 1). The number of patients completing all chemotherapy prescribed was roughly equivalent in both the IDS (23/38 patients, 61%) and PCRS (17/29 patients, 59%) groups. (In the IDS group, three patients were prescribed only three cycles.)The number of patients completing six cycles of chemotherapy was also similar between the groups (IDS 53%, PCRS 59%). Overall, 75% (295/393) of IP cycles were successfully administered. Grade 1 to 2 chemotherapy toxicities for both IDS and PCRS patients are detailed in Table 4. The most frequent toxicities (> 25%) in the IDS group were peripheral neuropathy (55%), fatigue (42%), nausea (42%), and neutropenia (29%). Frequent toxicities in the PCRS group were nausea (48%), peripheral neuropathy (41%), fatigue (34%), constipation (34%), abdominal pain (34%), and acute renal failure (28%). The most common Grade 3 to 4 toxicity was neutropenia, which was observed in 15% of patients overall (8 IDS, 2 PCRS). Other Grade 3 to 4 toxicities were rarely observed: peripheral neuropathy (1 IDS patient), abdominal pain (1 PCRS patient), and anemia (1 IDS patient). IP catheter complications were observed in 34% (23/67) of patients overall (Table 5). The most common complication in both groups was difficulty accessing the port, or no port access, which was observed in 11% and 21% of IDS and PCRS patients, respectively. Other complications included infection or cellulitis, port-site leakage, and peritonealvaginal fistula. In only one patient (PCRS) was a catheterinduced bowel perforation observed. This was noted on routine CT scan post chemotherapy. There were no catheterrelated complications in the four IDS patients who underwent bowel resection at the time of debulking surgery. In 27/67 patients (40%), IP chemotherapy was discontinued and treatment was switched to IV chemotherapy alone. The reasons for not receiving all prescribed IP chemotherapy are listed in Table 6. The majority of discontinuations were catheter-related (56%), including inability to access the
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Table 2. Patient characteristics

IDS (n = 38) Characteristic Median age (years) Range Histology Serous Endometrioid Clear cell Other FIGO stage II III IV Site of disease Ovary Peritoneum Fallopian tube Residual disease Microscopic < 1 cm Catheter insertion LUQ LLQ RUQ RLQ Unknown At time of surgery Postoperatively Radical surgery Bowel resection Splenectomy Diaphragm stripping
LLQ: left lower quadrant; LUQ: left upper quadrant; RLQ: right lower quadrant RUQ: right upper quadrant;

PCRS (n = 29) n (%) 56 3575 20 (69) 3 (10) 3 (10) 3 (10) 5 (17) 24 (83) 0 28 (97) 1 (3) 0 6 (21) 23 (79)

n (%) 61 3075 33 (87) 3 (8) 1 (3) 1 (3) 2 (5) 31 (82) 5 (13) 28 (74) 10 (26) 0 10 (26) 28 (74)

20 (53) 7 (18) 0 4 (11) 7 (18) 38 (100) 0 4 (11) 0 1 (3)

18 (62) 8 (28) 0 0 3 (10) 28 (97) 1 (3) 0 1 (3) 1 (3)

Intraperitoneal Chemotherapy for Advanced Ovarian and Peritoneal Cancers

Table 3. Number of IP chemotherapy cycles completed

IDS (n = 38) Cycles 0 1 2 3 4 5 6 n (%) 0 6 (16) 2 (5) 4 (11) 3 (8) 3 (8) 20 (53) PCRS (n = 29) n (%) 2 (7) 4 (14) 2 (7) 1 (3) 2 (7) 1 (3) 17 (59)

port, persistent infection, peritoneal-vaginal fistula, persistent port leak, abdominal pain, and large bowel perforation. In the IDS group, 15/26 patients (58%) who completed four or more cycles of IP chemotherapy have recurred (1 patient progressed while on IP chemotherapy). The median time to recurrence in this group was 11 months (range 329 months). Two patients have died from active progressive disease. For the 11/26 patients who have not had recurrence, the median follow-up time was 14 months (range 732 months). In the PCRS group, 7/20 patients (35%) who completed four or more cycles of IP chemotherapy have recurred (2 patients progressed while on IP chemotherapy). The median time to recurrence in this group was 12 months (range 232 months). Two patients have died from active progressive disease. For the 13/20 patients who have not had recurrence, the median follow-up time was nine months (range 630 months).
DISCUSSION

Table 4. Grade 1 to 2 chemotherapy toxicity for IDS and PCRS patients

IDS (n = 38) Adverse event Anemia Neutropenia Peripheral neuropathy Fatigue Nausea Vomiting Constipation Abdominal pain Tinnitus Hypomagnesemia Acute renal failure n (%) 7 (18) 11 (29) 21 (55) 16 (42) 16 (42) 8 (21) 7 (18) 9 (24) 3 (8) 8 (21) 4 (11) PCRS (n = 29) n (%) 5 (17) 6 (21) 12 (41) 10 (34) 14 (48) 4 (14) 10 (34) 10 (34) 3 (10) 6 (21) 8 (28)

Our study is the first to report on the use of cisplatin-based IP chemotherapy in IDS patients. Secondly, it demonstrates a shorter median time to recurrence than might be expected with the use of IP chemotherapy (in both PCRS and IDS patients), compared with that described in previous trials. The patients in this study were similar demographically to recently published IP chemotherapy studies,6,9,10 in that most patients were aged 50 to 70 years with a diagnosis of stage III serous ovarian carcinoma. In all patients, optimal debulking was achieved prior to the commencement of IP chemotherapy and all but one patient had their IP port inserted at the time of surgery. The IP chemotherapy regimen used at the TBCC was based on that used in the GOG 172 trial,4 largely because of the significant survival benefit demonstrated in the trial. The only difference between the two regimens was that at TBCC 75 mg/m2 cisplatin IP was given on Day 1 as opposed to 100 mg/m2 cisplatin IP given on Day 2 in the study of Armstrong et al.4 Many centres have switched to using a lower dose of cisplatin IP in an attempt to reduce toxicity and improve patient tolerance. In a recent survey of IP practice patterns, 54% reported using cisplatin 75 mg/m2 IP, while only 37% said they used the 100 mg/m2 dose. Similar to our regimen, the majority reported administering paclitaxel 60 mg/m2 IP on Day 8.5 However, a recent report from Chin et al.9 described a one-day outpatient IP chemotherapy regimen using cisplatin 100 mg/m2 IP combined with paclitaxel 175 mg/m2 IV. In this study, 74% of patients completed their planned course of IP/IV chemotherapy with an acceptable toxicity profile.9 In our study, the six-cycle completion rate for both IDS (53%) and PCRS
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Table 5. Catheter-related complications

IDS (n = 38) Adverse event Difficult/impaired access Infection/cellulitis Port-site leaking Peritoneal-vaginal fistula Bowel perforation n (%) 4 (11) 3 (8) 1 (3) 2 (5) 0 (0) PCRS (n = 29) n (%) 6 (21) 1 (3) 3 (10) 1 (3) 1 (3)

GYNAECOLOGY

(59%) groups was superior to those reported both in GOG 1724 (42%) and in a recent study by Berry et al.10 using docetaxel IV and cisplatin/paclitaxel IP, in which only 29% of patients completed six cycles. It is difficult to compare our chemotherapy completion results to those of Chin et al.9 because they did not give paclitaxel IP on Day 8; it is unclear how this might have influenced the tolerability of their regimen. In the only other study to report on the use of IP chemotherapy in IDS patients, in which carboplatin was substituted for cisplatin in a Day 1/Day 8 regimen, Tiersten et al.6 reported a six-cycle completion rate of 69%. Despite the fact that the IDS and PCRS groups were different in terms of the extent of peritoneal disease prior to treatment and use of neoadjuvant chemotherapy, the ability to tolerate the IP chemotherapy regimen (based on the six-cycle completion rate) was similar between the groups. Frequent (> 25%) Grade 1 to 2 chemotherapy toxicities observed in both the IDS and PCRS groups included fatigue, peripheral neuropathy, and nausea. These and other side-effects are common and have been reported elsewhere.3,9,10 The most common Grade 3 to 4 toxicity encountered in our study was neutropenia, occurring in 15% of patients overall (8 IDS, 2 PCRS). This result was equivalent to that observed in the study of Chin et al.,9 but markedly less than those seen in GOG 172 (76%)4 and in the study by Berry et al. (43%).10 Catheter complications were not infrequent in our study, occurring in 34% (23/67) of patients. As was the case in GOG 172,4,11 the main reason for discontinuing IP chemotherapy was catheter-related (56%). Difficulty accessing the port or no port access was the most common problem encountered in both the IDS (11%) and PCRS (21%) patients, and this was likely related to catheter location. In our early experience, a number of the IP ports were placed in the left and right lower quadrants, but this led to internal rotation of the reservoir, limiting access of the Huber needle. It is now our procedure to place all ports 2 to 3 cm above the left costal margin in the midclavicular line. The median time to recurrence in those patients who completed four or more cycles of IP chemotherapy in the IDS and PCRS groups was 11 and 12 months, respectively. While it is difficult to compare our data directly, the PFS reported in previous trials (2429 months)3,4,6 is roughly twice the median time to recurrence reported herein, and may be cause for concern. There are several possible explanations for the discrepancy in results. First, our study is limited by its retrospective design, small sample size, and short follow-up period. Because of these limitations, it was not possible to calculate PFS and OS reliably for our data set. Instead, median time to recurrence was chosen as a surrogate for PFS. Traditionally, PFS has been defined as the
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Table 6. Reasons for not receiving all prescribed IP chemotherapy (n = 27)

Adverse event Catheter-related (56%) Poor access/could not access port Persistent infection Peritoneal-vaginal fistula Persistent port leak Abdominal pain Other (44%) Large bowel perforation Acute renal failure Bone marrow suppression Patient requesting switch to IV Progressive disease Perforated duodenal ulcer Nurse administration error Ototoxicity Nausea/vomiting 1 2 2 2 2 1 1 1 1 4 3 3 2 2 n

time until progression, death, or the date of last contact, whichever came first.4 Another possible explanation for the discrepancy in results pertains to the number of cycles of IP chemotherapy received. In GOG 172, only 107/205 patients (52%) received four or more cycles of IP chemotherapy4 compared with 46/67 (69%) in this study. We chose to calculate recurrence data for those patients receiving at least four cycles in order to reflect the benefit received from IP chemotherapy more accurately. Additional study will be required to examine the effect of the duration of treatment on clinical outcome. Finally, all studies under comparison used different treatment regimens. One possible explanation for the difference in outcome may relate to the dose of cisplatin used or whether carboplatin should be substituted for cisplatin. Results from the Scottish Gynaecologic Clinical Trials Group showed improved overall survival with cisplatin 100 mg/m2 IV versus 50 mg/m2 IV in women with advanced ovarian cancer.12 Other trials, however, have failed to demonstrate a significant survival difference with increasing cisplatin dose in suboptimally debulked patients.13,14 With respect to the use of carboplatin IP and paclitaxel on Day 8, two follow-up

Intraperitoneal Chemotherapy for Advanced Ovarian and Peritoneal Cancers

trials to GOG 172 are planned to attempt to answer this question. 15,16
CONCLUSION

7. Vergote I, Trope CG, Amant F, Kristensen GB, Sardi JE, Ehlen T, et al. EORTC-GCG/NCIC-CTG randomized trial comparing primary debulking surgery with neoadjuvant chemotherapy in stage IIIC-IV ovarian, fallopian tube and peritoneal cancer. Plenary presentation at the 12th biennial meeting International Gynecologic Cancer Society IGCS, Bangkok, Thailand, October 2528, 2008 (abs.). 8. Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Available at: http://evs.nci.nih.gov/ftp1/CTCAE/About.html. Accessed June 1, 2009. 9. Chin SN, Pinto V, Rosen B, Oza A, Dodge J, Murphy J, et al. Evaluation of an intraperitoneal chemotherapy program implemented at the Princess Margaret Hospital for patients with epithelial ovarian carcinoma. Gynecol Oncol 2009;112:4504. 10. Berry E, Matthews KS, Singh DK, Buttin BM, Lurain JR, Alvarez RD, et al. An outpatient intraperitoneal chemotherapy regimen for advanced ovarian cancer. Gynecol Oncol 2009;113:637. 11. Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, et al. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study. Gynecol Oncol 2006;100:2732.12. 12. Kaye SB, Paul J, Cassidy J, Lewis CR, Duncan ID, Gordon HK, et al. Mature results of a randomized trial of two doses of cisplatin for the treatment of ovarian cancer. Scottish Gynecology Cancer Trials Group. J Clin Oncol 1996;14:21139. 13. Conte PF, Bruzzone M, Carnino F, Gadducci A, Algeri R, Bellini A, et al. High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ouest. J Clin Oncol 1996;14:3516. 14. McGuire WP, Hoskins WJ, Brady MF, Homesley HD, Creasman WT, Berman ML, et al. Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 1995;13:158999. 15. Walker JL. Intraperitoneal chemotherapy for ovarian cancer: 2009 goals. Gynecol Oncol 2009;112:43940. 16. An NCIC (National Cancer Institute of Canada) CTG led GCIG Study. A phase II/III study of intraperitoneal (IP) plus intravenous (IV) chemotherapy versus IV carboplatin plus paclitaxel in patients with epithelial ovarian cancer optimally debulked at surgery following neoadjuvant intravenous chemotherapy. Presented at the NCIC spring meeting, April 2009.

Although our study demonstrates that IP chemotherapy is feasible and well-tolerated in IDS patients as well as in PCRS patients, the regimen employed at TBCC shows a median time to recurrence that is shorter than expected based on information reported in previous trials. This may be cause for concern, as recent evidence shows that many practitioners have adopted an IP chemotherapy regimen similar to that employed in our study.
REFERENCES
1. United States National Institutes of Health. Clinical advisory: NCI issues clinical announcement for preferred method of treatment for advanced ovarian cancer. Available at: http://www.nlm.nih.gov/databases/ alerts/ovarian_ip_chemo.html. Access May 15, 2009. 2. Alberts DS, Liu PY, Hannigan EV, OToole R, Williams SD, Young JA, et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 1996;335:19505. 3. Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol 2001;19:10017.4. 4. Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006;354:3443.5. 5. Naumann R, Sukumvanich P, Edwards R. Practice patterns of intraperitoneal chemotherapy in women with ovarian cancer. Gynecol Oncol 2009;114(1):3741. 6. 6. Tiersten AD, Liu PY, Smith HO, Wilczynski SP, Robinson WR III, Markman M, et al. Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009. Gynecol Oncol 2009;112:4449.

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