paywalled: Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis.

Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis.:

Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis.

Hepatogastroenterology. 2012 Jul-Aug

Abstract
Background/Aims:
We conducted a phase I trial of IP oxaliplatin and paclitaxel with IV paclitaxel and bevacizumab in patients with peritoneal carcinomatosis.

Methodology:
Patients received IV bevacizumab (2.5mg/kg) over 1 hour (day 1), then IV paclitaxel (110mg/m2) 24-hr-infusion (day 1) and IP oxaliplatin (25-40mg/m2) (day 2), and IP paclitaxel (30-60mg/m2) (day 8 from cycle 2 onwards). A '3+3' design was used.

Results:
Nineteen patients were treated (median age 60 years; 10 women, 9 men; median number of prior therapies 3). Primary tumors were colorectal (n=9), signet ring carcinoma (n=2), gastric (n=2), ovarian (n=2) and others (n=4). The maximum tolerated doses (MTD) of IP oxaliplatin and IP paclitaxel were 25mg/m2 and 60mg/ m2, respectively. Nine (47%) patients reported no toxicities >grade 2. Two patients receiving IP oxaliplatin 40mg/m2 and IP paclitaxel 60mg/m2 had dose limiting toxicities (DLT) of grade 3 diarrhea/dehydration and febrile neutropenia. Toxicities included abdominal pain (n=14), nausea (n=10) and constipation (n=7). Of 12 patients restaged at 2 months, 7 (58%) had stable disease (SD) including 2 (17%) who had SD for >4 months.

Conclusions: 
IP paclitaxel and IP oxaliplatin can be given safely at 60mg/m2 and 25mg/m2, respectively.

PMID: 22580643 [PubMed - in process]

abstract: Regimens with intraperitoneal cisplatin plus intravenuous cyclophosphamide and intraperitoneal carboplatin plus intravenuous cyclophosphamide are equally effective in second line intraperitoneal chemotherapy for advanced ovarian cancer.

Regimens with intraperitoneal cisplatin plus intravenuous cyclophosphamide and intraperitoneal carboplatin plus intravenuous cyclophosphamide are equally effective in second line intraperitoneal chemotherapy for advanced ovarian cancer.:


Abstract
Purpose:
We compared response, survival and side effects of regiments with intravenous cyclophosphamide followed by intraperitoneal cisplatin versus intravenous cyclophosphamide followed by intraperitoneal carboplatin as second line treatment in one center retrospective study.

Material and Methods:
Inclusion criteria were: relapse or recurrence of the disease after surgery and first line treatment; stage III histologicaly documented serous epithelial ovarian cancer after one or more prior regiments of chemotherapy. Recurrence were confirmed throughout restaging laparotomy or second look laparotomy. Patients from one of the groups received 90mg/m2 cisplatin on the first day and 750mg/m2 cyclophosphamide intravenously, while the second group members AUC 6 carboplatin intraperitoneally and 750mg/m2 cyclophosphamide intravenously. Four courses were administrated for each patient.

Results: 

Of the 49 patients in the cisplatin group the response rates were 21 (43%), 10 (20%) and 18 (37%) in the groups of pathologic complete response, pathologic partial response and progressive disease, respectively. The median survival from the initiation of intraperitoneal chemotherapy was 59 months.

Of the 25 patients in the carboplatin group the response rates were 10 (40%), 4 (16%) and 11 (44%) respectively. The median survival -51 months.

The differences between the groups were not statistically significant p 0.05 either in response or in toxicity.

Conclusions: 
The results of our research including relatively long survival from intraperotoneal chemotherapy initiation confirm that carboplatin treatment is as good as cisplatin in second line intraperitoneal chemotherapy for ovarian cancer.

open access: Ports and complications for intraperitoneal chemotherapy delivery (ovarian cancer)

"Intraperitoneal access ports are essential to the delivery of chemotherapy agents into the peritoneal cavity of women with ovarian cancer, but their malfunction and adverse effects are frequently responsible for the failure to complete planned therapy. Complications, such as obstruction of the catheter, infection, leakage, rotation, retraction, and pain, together with bowel and vaginal perforation, cause delays in treatment, patient suffering and the expenditure of medical resources. A wide variety of ports have been used, including vascular access devices and intraperitoneal access devices. This paper reviews the development and use of ports for intraperitoneal chemotherapy, their complications and reported methods of prevention...."

(Blogger's Note: tables are included in the text of the paper)

Table 2.   Reported complications of ports used for IP access 
(years 1984 through to 2010)

Table 3.   Percentage of cases where IP chemotherapy was discontinued because of the port 
(years 1994 through to 2010)

Table 4.   Port complications causing the discontinuation of IP chemotherapy* 
(years 1991 through to 2010)

	Influence of surgeon and team experience "There is a lack of information in the literature with regard to the effect of the expertise of the surgeon placing the ports, and the experience of the support team (including doctors and nurses) in managing the ports and patients to reduce complications and improve completion rates...."

		Conclusion:

Port complications are significant, and overall, 15% (210/1945) of patients discontinued IP chemotherapy as a result of a port complication, with obstruction (37.6%) and infection (31.4%) being the most common reasons.

Complications such as leakage, retraction of the catheter, rotation of the portal, difficulties with access and perforation of the bowel can be kept to a minimum with careful technique, but they are still not completely avoidable. Although infection may theoretically be reduced by the avoidance of placement during grossly contaminated surgeries, hard data on the influence of associated bowel surgery at the time of placement are lacking, and there is no proven method of preventing the adhesions that cause obstruction to flow. There does not appear to be a difference in the rates of complications between fenestrated or unfenestrated ports, and the choice of port should be at the surgeon’s discretion.

Despite almost 30 years of experience, it remains difficult to identify which patients are going to experience port complications that impact on the completion of IP therapy. More effective methods of preventing complications and improving tolerability, and thus reducing discontinuation rates, are needed.

Intravenous/Intraperitoneal Paclitaxel and Intraperitoneal C... : International Journal of Gynecological Cancer

Objective:
This study aimed to evaluate intravenous (IV)/intraperitoneal (IP) paclitaxel and IP carboplatin (TCipTip therapy) feasibility in epithelial ovarian (EOC), fallopian tube (FTC), or peritoneal carcinoma (PC) patients.


Methods:
From December 2007 to August 2010, 20 women with histologically confirmed stage IC to IV EOC, FTC, or PC.....

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: A Gynecologic Oncology Group study

Highlights

► The maximum tolerated dose and feasibility of IV and IP chemotherapy was assessed.
► The dose limiting toxicity rate for Paclitaxel 175 mg/m² IV, carboplatin AUC 6 IP and paclitaxel IP was 35%.

Patterns of first recurrence following adjuvant intraperitoneal chemotherapy for stage IIIC ovarian cancer

blogger's note:

Table 2. Site of first recurrence.
Table 3. Pattern of first recurrence

"In conclusion, patients treated with adjuvant IP chemotherapy appear to have a different pattern of disease recurrence than patients treated with IV chemotherapy. The locations of these recurrences reflect the ability of IP chemotherapy to successfully eradicate disease within the anatomic regions of drug distribution.
Recurrent disease outside the abdominal cavity can be anticipated to occur more frequently in the current era of primary IP chemotherapy.
Further efforts should be aimed at improving IP distribution of chemotherapy to areas that may become disease sanctuaries."

Laparoscopic Intraperitoneal Port Placement for Optimally Cytoreduced Advanced Ovarian Cancer

full free access: Phase ii/iii study of intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian cancer: Canada

Note:

1) see Section 2.3 for study criteria (patient enrollment requirements);
2) .... acquisition of tumour specimens both before study therapy is started and after neoadjuvant chemotherapy has been received provides a unique opportunity for a correlative study of differing drug responses within the same patients.

Although the study is led by the ncic ctg, the protocol, the accompanying IP therapy guidelines, and a companion document intended to summarize and promote best practice in the administration of IP therapy are the result of a collaboration between the ncic ctg and the Society of Gynecologic Oncologists of Canada, with international partners in the United Kingdom (National Cancer Research Institute), Spain (Spanish Ovarian Cancer Research Group), and the United States (Southwest Oncology Group).

Abstract: (including full free text access):

full free access (pdf): A phase I study with an expanded cohort to assess the feasibility of intraperitoneal carboplatin and intravenous paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: A Gynecologic Oncology Group study

Research Highlights

► The MTD (maxium tolerated dose) of IP carboplatin with IV paclitaxel (175 mg/m²) was an AUC 8.
►IP carboplatin can be given with IV paclitaxel over multiple cycles at an AUC 6.
►Dose-limiting toxicities of IP carboplatin were thrombocytopenia and leukopenia.

(no abstract) Peritoneal fibrosis leading to small bowel obstruction two years after first-line intraperitoneal chemotherapy for optimally debulked ovarian cancer Australian

DOI: 10.1111/j.1479-828X.2010.01230.x

Issue

Australian and New Zealand Journal of Obstetrics and Gynaecology

Volume 51, Issue 1, pages 91–92, February 2011

abstract: Ventral hernia following primary laparotomy for ovarian, fallopian tube, and primary peritoneal cancers

An incisional hernia occurs in an area of weakness caused by an incompletely-healed surgical wound. Since median incisions in the abdomen are frequent for abdominal exploratory surgery, ventral incisional hernias are termed ventral hernias. ...
en.wikipedia.org/wiki/Ventral_hernia

OBJECTIVES: To evaluate the incidence and risk factors for ventral hernia development following primary laparotomy for ovarian, fallopian tube, and peritoneal cancers.
CONCLUSIONS: The development of ventral hernia is a significant postoperative morbidity in patients undergoing primary surgery for ovarian, tubal, or peritoneal cancer. Independent associations with hernia development include: BMI and IP chemotherapy by Year 1, and BMI, wound complications and advanced stage by Year 2.

Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin: potential for consolidation in ovarian cancer.

Second-line treatment of first relapse recurrent ovarian cancer.Australian and New Zealand Journal of Obstetrics and Gynaecology abstract

Review Article

cytoreductive surgery • intraperitoneal chemotherapy • ovarian cancer
ABSTRACT

First-line therapy of advanced ovarian cancer involves primary cytoreductive surgery and adjuvant systemic chemotherapy. Progression of incompletely resected disease or recurrence after cytoreduction is inevitable. The approach to second-line treatment is ill-defined and chemotherapy remains the conventional approach, with surgery being reserved in some patients to debulk or palliate symptoms. Increasing evidence suggests that secondary cytoreduction improves progression-free and overall survival. This approach may be appropriate in selected patients. Intraperitoneal chemotherapy delivered in the adjuvant setting postoperatively has been shown to be more effective than systemic chemotherapy in advanced ovarian cancer after primary surgery. However, its use has not been well accepted and has not been adopted in secondary surgery. Hyperthermic intraperitoneal chemotherapy delivered intraoperatively during surgery has been of clinical interest and may prove to be efficacious and advantageous. The support of the gynaecological cancer medical and surgical community to embrace the efforts and assist in the recruitment of appropriate patients into randomised trials of first relapse recurrent ovarian cancer will provide answers to questions and establish evidence that would impact the care of ovarian cancer patients.

media item: Gynecologic Oncologists Advance Promising Intraperitoneal Approach - Carboplatin IP/phase 111 studies

"The present studies provide additional useful data on carboplatin and the feasibility of intraperitoneal infusion. Specifically, data relating to maximum tolerated dose and dose-limiting toxicity derived from these studies will be implemented in advanced phase-III research trials."

Markman: Intraperitoneal chemotherapy in the management of ovarian cancer: focus on carboplatin

article: http://www.dovepress.com/intraperitoneal-chemotherapy-in-the-management-of-ovarian-cancer-focus-peer-reviewed-article

open text pdf file: http://www.dovepress.com/getfile.php?fileID=4267

Worth noting:

Finally, as it is known that patients with “high risk”
early stage ovarian cancer have a 30% to 50% chance of
experiencing recurrence of the disease process, and those
recurrences are largely within the peritoneal cavity, it is
perhaps reasonable to consider delivering some, or perhaps
all, of a planned adjuvant chemotherapy approach via the
intraperitoneal route.