Administration Of Intravenous Chemotherapy Research Articles

Differences in Symptom Occurrence, Frequency, Intensity, and Distress in Adolescents Prior to and One Week After the Administration of Chemotherapy

The purpose of this study was to describe differences in occurrence, frequency, intensity, and distress of symptoms prior to (T1) and one week following (T2) the administration of intravenous chemotherapy. Longitudinal, descriptive. Two regional children's cancer centers in the Pacific Northwest. A total of 51 adolescents 10 to 19 years old receiving cancer chemotherapy. Memorial Symptom Assessment Scale (MSAS 7-12). No significant differences were found in symptom occurrence rates between T1 and T2. Fatigue was the only symptom with significantly greater frequency and intensity, and nausea was the only symptom with significantly greater distress at T2 compared with T1. Adolescents receiving chemotherapy experience multiple symptoms that persist over time. In monitoring for symptoms, nurses need to be aware of the extent to which symptoms are present throughout treatment, as evidenced by these findings that symptom occurrence was significant even prior to receiving a subsequent course of chemotherapy.

Hyperthermic intraperitoneal chemotherapy: Rationale and technique

The combination of complete cytoreductive surgery and perioperative intraperitoneal chemotherapy provides the only chance for long-term survival for selected patients diagnosed with a variety of peritoneal neoplasms, either primary or secondary to digestive or gynecologic malignancy. Hyperthermic intraperitoneal chemotherapy (HIPEC) delivered in the operating room once the cytoreductive surgical procedure is finalized, constitutes the most common form of administration of perioperative intraperitoneal chemotherapy. This may be complemented in some instances with early postoperative intraperitoneal chemotherapy (EPIC). HIPEC combines the pharmacokinetic advantage inherent to the intracavitary delivery of certain cytotoxic drugs, which results in regional dose intensification, with the direct cytotoxic effect of hyperthermia. Hyperthermia exhibits a selective cell-killing effect in malignant cells by itself, potentiates the cytotoxic effect of certain chemotherapy agents and enhances the tissue penetration of the administered drug. The chemotherapeutic agents employed in HIPEC need to have a cell cycle nonspecific mechanism of action and should ideally show a heat-synergistic cytotoxic effect. Delivery of HIPEC requires an apparatus that heats and circulates the chemotherapeutic solution so that a stable temperature is maintained in the peritoneal cavity during the procedure. An open abdomen (Coliseum) or closed abdomen technique may be used, with no significant differences in efficacy proven to date. Specific technical training and a solid knowledge of regional chemotherapy management are required. Concerns about safety of the procedure for operating room personnel are expected but are manageable if universal precautions and standard chemotherapy handling procedures are used. Different HIPEC drug regimens and dosages are currently in use. A tendency for concurrent intravenous chemotherapy administration (bidirectional chemotherapy, so-called "HIPEC plus") has been observed in recent years, with the aim to further enhance the cytotoxic potential of HIPEC. Future trials to ascertain the ideal HIPEC regimen in different diseases and to evaluate the efficacy of new drugs or drug combinations in this context are warranted.

Port central venous catheters–associated bloodstream infection during outpatient-based chemotherapy

Central venous catheters (CVCs) are commonly used for the administration of intravenous chemotherapy in outpatient setting. Nevertheless, outbreaks of catheter-associated bloodstream infections had been reported from oncology centers. We describe a large outbreak of CVCs-associated Klebsiella oxytoca bloodstream infection, occurring in an oncology chemotherapy outpatient unit of northern Greece between October 2006 and May 2007. The outbreak involved approximately 10% of the patients with CVCs who were receiving home-based chemotherapy, and it represents the second larger outbreak of CVCs-associated BSIs due to Klebsiella oxytoca in oncology outpatient centers. We retrospectively analyzed the chain of investigations and prophylactic/diagnostic measures taken to eradicate the infection: (1) patients' chart audit, (2) estimation of the infection among asymptomatic patients, (3) implementation of the level of awareness of medical and paramedical personnel, (4) collection of samples from environment, medications and infusion materials, (5) critical appraisal of chemotherapeutical schemes and (6) cooperation with peripheral institutions. The isolation of Klebsiella oxytoca in a chemotherapy solution (infusional 5-FU in dextrose 5% solution within a 48h pump) from a peripheral General Hospital and the prompt transmission of the data to the chemotherapy center played a key role for the management of the infection cluster. This is the first report that evidenced the detection of Klebsiella oxytoca within a chemotherapeutical preparation. Data transmission from peripheral hospitals to the central institution resulted in an important feedback that allowed a better estimation of the infection cluster and more tailored actions for the eradication of the infection.

Pharmacoeconomic analysis of capecitabine for advanced gastric cancer in Taiwan

15576 Background: Capecitabine combined with cisplatin (XP) is a safe and effective alternative to intravenous 5-fluorouracil plus cisplatin (FP) in previously untreated patients with advanced and metastatic gastric cancer (AGC). The objective of this pharmacoeconomic analysis was to access the cost-effectiveness of XP versus FP for AGC treatment from Taiwan societal perspective. Methods: A cost-minimization analysis was undertaken by applying clinical outcomes and medical resource utilization (MRU) retrieved from phase III ML17032 study. Direct medical costs associated with trial-based MRU were based on Taiwan's National Health Insurance fee schedule for 2007. Costs associated with intravenous chemotherapy administration and adverse event (AE) management were estimated by an expert panel survey conducted among 12 oncologists. From a societal perspective, direct non-medical and indirect costs borne by patients, such as travel and time costs, were also considered. One-way sensitivity analyses were performed on key model parameters by varying the input values by ± 10%. Results: A trend toward superior progression-free survival was observed in XP arm (median 5.6 months for XP versus 5.0 for FP). Compared to FP, administration of XP required fewer consults per patient (5.2 for XP versus 22.8 for FP). Chemotherapy drug cost was higher (USD$1,712) in the XP arm; however, these cost increments were offset by differences of chemotherapy administration costs (USD$4,376) between two arms. AE profiles were similar and the costs associated with grade 3/4 AE management were slightly lower (USD$30) in the XP arm. Taking into account direct medical costs (chemotherapy administration and AE management), direct non- medical cost (travel), and indirect cost (time), XP was associated with a significant cost saving of USD$5,310 (NTD$172,197). XP remained cost-saving under one-way sensitivity analyses. Conclusions: Given the trend to superior efficacy, the significant cost savings, and the convenience of oral treatment, XP would be a dominant (less costly and more effective) regimen for AGC from the Taiwan societal perspective. Replacing FP by XP would not only reduce health care expenditures but also improve health outcomes in Taiwan. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration F. Hoffmann-La Roche AG, Roche Taiwan

Costs associated with intravenous chemotherapy administration in patients with small cell lung cancer: a retrospective claims database analysis

ABSTRACTObjectives: With new oral chemotherapy drugs emerging, it is useful to understand the costs associated with traditional intravenous (IV) therapy. This study aims to assess costs associated with IV chemotherapy in patients with small cell lung cancer (SCLC) from the perspective of large employer-payers.Study design: Descriptive retrospective claims database analysis.Methods: Using medical claims data from 5.5 million beneficiaries between 01/01/1998 and 01/31/2006, we identified patients with lung cancer (ICD-9 codes 162.3–162.9, 176.4, or 197.0) who received IV chemotherapy. A case-finding SCLC algorithm was then applied which selected patients who were treated with chemotherapies commonly used in SCLC (cisplatin/etoposide, cis­platin/irinotecan, carboplatin/etoposide, topotecan, or cyclophosphamide/doxorubicin/vincristine) and then excluded those who had treatments or procedures indicative of non-small cell lung cancer (NSCLC) (positron emission tomography [PET] scan imaging, lung surgery, common NSCLC chemotherapies). Average total costs paid per day of IV chemotherapy administration were computed, along with separate costs for IV chemotherapy drugs, IV chemotherapy administration procedures, and other drugs and services received on IV visit days. Costs were also estimated per course of treatment based on the assumption of four chemotherapy cycles per course with three visits per cycle.Results: Among 8010 patients with a lung cancer diagnosis, 802 were identified as SCLC. In the SCLC subset, the average total daily cost was $787 ($9449/course), with $395 ($4742/course; 50.2%) attributable to IV chemotherapy drugs, $93 ($1112/course; 11.8%) to IV chemotherapy administration, and $300 ($3595/course; 38.0%) to other drugs and services.Conclusions: The proposed algorithm identified about 10% of patients with lung cancer receiving IV chemotherapy as likely SCLC cases. Future studies should validate this algorithm with medical records data. IV chemotherapy administration and other visit-related drugs and services represented about half of the total cost per IV visit day, with the remainder attributable to direct costs for IV chemotherapy drugs.

P1-223: Costs associated with intravenous chemotherapy administration in patients with lung cancer

P1-223: Costs associated with intravenous chemotherapy administration in patients with lung cancer

Costs associated with intravenous (IV) chemotherapy administration in patients with lung cancer

18092 Background: The IV method of chemotherapy administration imposes not only a time burden on patients and facilities, but also has cost implications for payers. This study aims to assess the costs associated with the IV administration of chemotherapies for patients with all forms of lung cancer and for a subset of patients with small cell lung cancer (SCLC) in a large employer-payer claims database. Methods: Using medical claims data from 5.5 million beneficiaries between 01/01/1998 and 01/31/2006, we identified 8,605 patients with lung cancer (ICD-9 codes 162.3–162.9, 176.4, or 197.0) receiving IV chemotherapies. We then identified a subset of 942 patients likely to have SCLC by selecting those receiving chemotherapy regimens primarily used to treat SCLC and excluding patients receiving procedures and treatments often associated with NSCLC. Average total costs per day of IV chemotherapy administration (including drug, administration costs, etc.) were computed for all patients and for the SCLC subset based on the actual amount paid. Costs were also computed separately for: IV chemotherapy drugs, IV chemotherapy administration procedures, and other drugs and services such as IV administration of other drugs to treat side effects of chemotherapies, evaluation and management, and laboratory tests. Results: Average total cost per day of IV chemotherapy administration for all patients was $1,112, with $652 (59%) attributable to IV chemotherapy drugs, $85 (8%) to IV chemotherapy administration procedures, and $375 (34%) to other drugs and services. Among patients with SCLC, average total daily cost was $815, with $423 (52%) attributable to IV chemotherapy drugs, $89 (11%) to IV chemotherapy administration, and $303 (37%) to other drugs and services. Conclusions: IV chemotherapy administration procedures and other visit-related services accounted for 42% and 48% of total costs in patients with all forms of lung cancer and those with SCLC, respectively. The increased availability and use of oral chemotherapy drugs in lung cancer should provide savings to payers by avoiding the costs associated with IV administration. No significant financial relationships to disclose.

The effect of ultrasonic irradiation on doxorubicin-induced cytotoxicity in three human bladder cancer cell lines

Although ultrasonic irradiation has been proven to increase membrane permeability and enhance chemotherapeutic cytotoxicity in a number of cell lines, this effect has never been demonstrated in bladder cancer cells. Bladder cancer may offer a unique setting for ultrasound enhancement of chemotherapy, since intravesicular rather than intravenous administration of chemotherapy is used in superficial cases. The aim of this study was to investigate whether a non-toxic dose of ultrasound could increase membrane permeability, and potentiate the cytotoxicity of doxorubicin to three human bladder carcinoma cell lines (TCC–SUP, T24, and RT4) in vitro. An EuTDA–Efflux assay, which measures the amount of a chemical that is allowed to seep out of labeled cells, was used to analyze membrane permeability, and an MTS assay, which directly measures cell viability, was used to determine the effect of chemotherapy on cells after they were treated with a variety of doxorubicin concentrations and ultrasonic exposures. Ultrasound treatment for 5min and 10min at an intensity of approximately 0.3W/cm2 resulted in a significant increase in EuTDA efflux in all three cell lines. However, no ultrasonic enhancement of doxorubicin growth inhibition in these human bladder carcinoma cells was observed. This suggests that either ultrasound does not increase doxorubicin uptake by the cell or that doxorubicin uptake is increased but in insufficient amounts to affect growth inhibition. Further investigation should focus on explaining these results.

A Role for Hepatic-Directed Chemotherapy in Colorectal Liver Metastases

Recent advances in the systemic therapy of colorectal cancer seem to have made regional therapy of hepatic metastases passe. Although regional therapy of hepatic metastases from colorectal cancer can produce high response rates with control of liver disease, there seems to be minimal impact on survival because of development of limiting extrahepatic disease. Why bother with the complexities of regional treatment requiring a major surgical procedure and possessing a unique toxicity, biliary sclerosis, when intravenous chemotherapy administration can achieve a high response rate and improved survival by treating extrahepatic as well as hepatic cancer? Perhaps hepatic arterial therapy is best viewed as a potentially useful debulking technique for colorectal liver metastases with negligible effect on occult extrahepatic disease. That consideration is evident in the three studies reported by Kemeny et al, 1 Ducreux et al, 2 and Faynsod et al 3 in this issue of theJournal of Clinical Oncology. All three studies attempt to overcome the shortcomings of regional therapy by addressing the therapy of extrahepatic disease and the biliary toxicity accompanying hepatic arterial infusions (HAI) of floxuridine (FUDR). The results of the phase I trial by Kemeny et al 1 from the Memorial Sloan-Kettering Cancer Center reported in this issue concerning the treatment of unresectable colorectal liver metastases are extremely positive. In this trial, all patients had implantation of a hepatic arterial catheter and pump and received either a set fixed dose of HAI FUDR (with dexamethasone to diminish biliary toxicity) plus systemic (intravenous) oxaliplatin plus irinotecan (group A) or oxaliplatin plus fluorouracil with leucovorin (group B). In group A, oxaliplatin and irinotecan were escalated separately to determine the maximum-tolerated dose (MTD) of the combination. In group B, dose levels of a 48-hour infusion of fluorouracil were escalated to the MTD, with oxaliplatin held at a conventional dose level. The study successfully defined the MTD for each group. Systemic chemotherapy doses at MTD were within the usual dose range for group A, but the fluorouracil dose was lower in group B. Toxicities were as expected and primarily related to the systemic treatment, and there were no cases of bilirubin elevation noted at MTD. Although this was a phase I study and involved only 36 patients, the response rates and survivals that were achieved were excellent. The complete plus partial response rate was 90% and 87% for groups A and B, respectively. For groups A and B, the median survival from pump placement was 36 and 22 months, respectively, and the median survival from diagnosis of liver metastases was 47 and 35 months, respectively. The patients included in the study were highly selected and had unresectable hepatic metastases with no extrahepatic disease and, in most instances (89% of patients), had experienced failure with undefined previous systemic chemotherapy. It is of interest to examine these results with those reported for similar systemic regimens in the initial treatment of colorectal cancer metastatic to multiple sites including the liver. The results in group A compare favorably with the previously reported response rate and median survival for combined systemic irinotecan and oxaliplatin of 35% and 17.4 months, respectively. 4 The outcome in group B compares well with the response rate of 54% for initial systemic treatment with oxaliplatin plus fluorouracil and leucovorin. 5 Overall survival time in the Kemeny et al 1 HAI study of 35 to 47 months exceeds the approximately 21-month overall median survival time for sequential oxaliplatin plus fluorouracil and leucovorin and for irinotecan plus fluorouracil and leucovorin in previously untreated patients. 5 The response rate for the combination of HAI FUDR and systemic chemotherapy seems higher than what would be anticipated for either type of therapy alone, suggesting that the benefits of HAI FUDR may be additive to systemic therapy. The results of this small, phase I study of HAI FUDR plus systemic therapy require confirmation in larger, multicenter, phase III trials.

Vascular Access Devices: A Patient's Perspective

Abstract Various vascular access devices are available and widely used in the hospital and home setting for the treatment of patients with acute and chronic illnesses. Many cancer patients, in particular, require Short- or long-term central venous access for the intravenous administration of chemotherapy, immunotherapy, blood products, antibiotics, total parental nutrition, and other medications. This author, a breast cancer survivor and a nurse, examines the benefits and drawbacks of venous access devices, the satisfaction and dissatisfaction with their use, and the effects these devices have on treatment and quality of life from a patient's perspective.

Vascular Access Devices: A Patient's Perspective

Various vascular access devices are available and widely used in the hospital and home setting for the treatment of patients with acute and chronic illnesses. Many cancer patients, in particular, require Short- or long-term central venous access for the intravenous administration of chemotherapy, immunotherapy, blood products, antibiotics, total parental nutrition, and other medications. This author, a breast cancer survivor and a nurse, examines the benefits and drawbacks of venous access devices, the satisfaction and dissatisfaction with their use, and the effects these devices have on treatment and quality of life from a patients perspective.

Association of total dose intensity of chemotherapy in primary central nervous system lymphoma (human non-acquired immunodeficiency syndrome) and survival.

The importance of enhanced drug delivery in patients with central nervous system (CNS) malignancies has not yet been demonstrated conclusively. Intra-arterial chemotherapy in combination with osmotic bloodbrain barrier disruption (BBBD) increases drug delivery to tumor by 2- to 5-fold and to surrounding brain tissue by 10- to 100-fold as compared with intravenous administration of chemotherapy. Primary CNS lymphoma (PCNSL) is an excellent model for studying dose intensity because PCNSL is a highly infiltrative, chemosensitive, primary CNS malignancy in which the integrity of the blood-brain barrier is highly variable. Survival time was assessed in 74 non-acquired immunodeficiency syndrome patients with PCNSL who underwent a total of 1047 BBBD procedures. Total dose intensity is estimated by using the number of intraarterial infusions or a cumulative degree of BBBD score. Using proportional hazards multivariable analyses to adjust for baseline characteristics, survival was significantly associated with the total intensity of BBBD (P < 0.05). Additional statistical analyses demonstrate that survival bias does not fully explain these associations. Even when only patients who attained a complete response are considered, increased dose intensity resulted in increased survival. In patients with PCNSL, a chemotherapy-responsive tumor type, survival time is highly associated with total drug dose delivered, even in analyses designed to control for potential survival biases. These results probably constitute the strongest evidence to date of the importance of total dose intensity in treating CNS malignancies.

Multi-targeted antifolate (MTA): pharmacokinetics of intraperitoneal administration in a rat model

Aims LY 231514 or MTA is a multi-targeted antifolate which has been used as an anticancer drug. It is an analogue of folic acid which has shown antitumour activity against various malignancies, particularly mesothelioma and colon cancer. For cancers with peritoneal surfaces extension, the advantage of intraperitoneal chemotherapy over intravenous chemotherapy administration is the high drug concentration that can be achieved locally. Using a rat model, this study was designed to compare the pharmacokinetics and tissue adsorption of intraperitoneal vs intravenous MTA. Methods Sprague–Dawley rats were randomized into three groups according to dose and route of delivery of chemotherapy (10 mg/kg: intravenous; 10 mg/kg: intraperitoneal; 100 mg/kg: intraperitoneal). During the course of the experiment, peritoneal fluid and blood were sampled using a standardized protocol. At the end of the 3 hour procedure the rats were sacrificed, all urine was extracted and selected tissue samples were taken. One additional rat was studied over a 6 hour period for each group. The concentration of MTA in all samples was determined by high performance liquid chromatography (HPLC). Results When MTA was delivered at 10 mg/kg the area under the curve (AUC) of the peritoneal fluid was significantly higher with intraperitoneal administration (10 778 μg/ml×min) compared to intravenous administration (454 μg/ml×min) (P<0.0001). This represents a 24-fold increase in exposure for tissues at peritoneal surfaces after intraperitoneal administration. The AUC ratio (AUC peritoneal fluid/AUC plasma) was 40.8 for intraperitoneal delivery as opposed to 0.014 for intravenous delivery (P=0.0063). The AUC ratio for intraperitoneal MTA at 100 mg/kg was 19.2. The half-life of MTA in the peritoneal fluid after intraperitoneal infusion was approximately 2 hours. There was a significant difference in MTA concentration in the mesenteric nodes and the abdominal wall (P=0.0036 and 0.0017) and in the kidneys (P=0.0122) when intraperitoneal and intravenous administration were compared. Other tissue samples did not demonstrate any difference in drug concentration. Conclusion These experiments demonstrated that the exposure of peritoneal surfaces to MTA is significantly increased with intraperitoneal MTA administration. Due to the high likelihood of microscopic residual disease after resection of intra-abdominal malignancies, clinical studies to evaluate intraperitoneal MTA may be indicated.

Patients' sensory experiences before, during and immediately following the administration of intravenous chemotherapy

Preparatory sensory information is essential for cancer patients receiving chemotherapy. Accurate sensory information prepares them for the sounds, sights, and sensations that they will encounter before during, and after treatment. This study investigates and describes the sensory perceptions and coping styles of cancer patients receiving chemotherapy, and compares the results with those reported from studies conducted in the USA. The data were collected through telephone interviews using the Sensory Information Questionnaire (Rhodes et al 1994). Following the presentation of the findings, the article concludes by making recommendations to reduce patients' anxiety during outpatient administration of chemotherapy.

The role of implantable central venous access devices (CVAD) in the administration of intravenous chemotherapy to patients with gynecologic malignancies

The role of implantable central venous access devices (CVAD) in the administration of intravenous chemotherapy to patients with gynecologic malignancies