Pharmacologic rationale for treatments of peritoneal surface malignancy from colorectal cancer

Table 1 Molecular weight and area under the curve ratios of intraperitoneal exposure to systemic exposure of chemotherapeutic agents used to treat peritoneal carcinomatosis

Drug	Molecular weight (Daltons)	Area under the curve ratio
5-fluorouracil	130.08	250
Carboplatin	371.25	10
Cisplatin	300.1	7.8
Docetaxel	861.9	552
Doxorubicin	579.99	230
Etoposide	588.58	65
Floxuridine	246.2	75
Gemcitabine	299.5	500
Irinotecan	677.19	N/A
Melphalan	305.2	93
Mitomycin C	334.3	23.5
Mitoxantrone	517.41	115-255
Oxaliplatin	397.3	16
Paclitaxel	853.9	1000
Pemetrexed	597.49	40.8

N/A: Not available.

Table 2 Variables influencing the response of peritoneal carcinomatosis to perioperative chemotherapy

Temperature	Increase in temperature above 37°C augments the cytotoxicity of cancer chemotherapy
Dose of intraperitoneal chemotherapy	As the dose increases the penetration of chemotherapy into cancerous tissue increases because of an increasing diffusion gradient
Distribution of chemotherapy solution and heat (open vs closed technique)	The open technique allows more uniform distribution of heat and chemotherapy solution because of the manual mixing of the abdominal and pelvic contents with the warm fluid
Timing of chemotherapy in relation to the timing of the surgical intervention	Using the chemotherapy with surgery allows complete distribution immediately after the total lysis of abdominal adhesions. This allows complete treatment of all peritoneal surfaces
Type of carrier solution	High molecular weight carrier solutions remain within the peritoneal cavity for a longer time period. The artificial ascites maintains the cancer chemotherapy in a large volume of fluid for an extended time period
Pressure	Pressure will increase the penetration of fluid and chemotherapy solution into normal and cancerous tissue
Volume of carrier solution	Increasing the volume of carrier solution without increasing the amount of chemotherapy will decrease the effectiveness of the treatment by lowering the diffusion gradient between the peritoneal space and the surrounding normal and cancerous tissue
Duration of instillation	Increasing the time period over which cancer chemotherapy is present within the peritoneal cavity will increase the cytotoxic effect
Vasoactive agents	Vasoactive agents will cause constriction of normal capillaries, but will not cause constriction of vessels within cancerous tissue. This will cause the chemotherapy to remain longer in the peritoneal space
Macromolecular vehicles	Coating of cancer chemotherapy by macromolecules may preferentially direct their entrance into cancerous tissue as compared to normal tissue
Drug sensitivity of the tumor	Increased responses are expected if the cancer is sensitive to the chemotherapy
Size of residual tumor nodules	The penetration of cancer chemotherapy is limited to approximately 1 mm. Therefore, large nodules greater than 1 or 2 mm in diameter will not be penetrated by intraperitoneal chemotherapy and should not be expected to be eliminated