Outpatient chemotherapy in gynecologic oncology

Gynecologic cancers have been mainly treated by surgery and radiotherapy. Recently, many antineoplastic medications are available and chemotherapy becomes an important therapeutic method in the treatment of cervical, endometrial and ovarian cancer. Platinum derivatives, taxanes, alkylating agents and irinotecan are usually used. Because these chemotherapeutic agents have many toxicities such as myelo-suppression, hypersensitivity reaction, nausea, vomiting and diarrhea, the treatment was scheduled for an inpatient setting. During the recent 10 years, new chemotherapeutic agents without severe toxicity were applied and effective supportive therapies to prevent toxicity were investigated. Under these conditions, chemotherapy in an outpatient setting is available and an Outpatient Chemotherapy Center was established at Kitasato University Hospital. Patients with gynecologic cancers mainly receive weekly chemotherapeutic regimen at the Outpatient Chemotherapy Center and the number is increasing gradually. For safe and comfortable outpatient chemotherapy, it is important to control regimens and to go into partnership with co-medicals.     

Outpatient oncology chemotherapy documentation tool.

Time-saving documentation tools are vital in today's patient care environment. One such tool was designed to facilitate charting of the wide variety of information generated during outpatient chemotherapy administration. It is anticipated that this tool eventually will be incorporated as a component of a quality assurance program.     

Metronomic dosing of chemotherapy: applications in pediatric oncology

Pediatric cancer has a better outcome profile than adult cancers. However, refractory disease and the potential for long-term morbidity resulting from the use of conventional therapies necessitate the development of novel treatments for this population. Recent advances in oncology include the use of low dose metronomic (LDM) chemotherapy. The promise of this novel therapeutic approach includes reduced toxicity and the potential for efficacy predominantly through an antiangiogenic effect. The clinical benefit may be realized especially when combined with other antiangiogenic agents and/or conventional maximally tolerated doses of chemotherapy. In this article, we review the evidence for the use of LDM chemotherapy with a focus on pediatric cancer. Included are some of the possible risks attributable to this therapy in a pediatric setting and some of the hurdles to overcome in order to conduct good clinical research. Emphasis is placed on the development of proper surrogate markers to monitor antiangiogenic therapy in order to both optimize the dosing schedule for LDM chemotherapy and to provide a way of tracking therapeutic efficacy.     

Outpatient cancer chemotherapy employing implantable systems]

Outpatient cancer chemotherapy (OCC) employing implantable systems was introduced and the objects, conditions and problems of OCC were discussed based on experiences in 324 cases. The aims of OCC are improved QOL and the continuation of chemotherapy. Our requirements are safety, effectiveness, easy management and non-disturbance of activity. Implantable systems are very useful for OCC, especially continuous infusion combined with ambulatory pumps. However, the improvement of ambulatory pumps and the establishment of methods to evaluate OCC are required to further develop OCC.     

Outpatient chemotherapy for advanced lung cancer]

We reviewed the records of outpatient chemotherapy for advanced lung cancer in our institution. Thirty-two patients received 122 courses of cisplatin-free chemotherapy as outpatient treatments. Before outpatient treatment, every patient received the first chemotherapy as an inpatient treatment and the dose of cytotoxic drugs was reduced accordingly when side effects were judged to be untolerable. Only 1 patient needed hospitalization because of pneumonia with grade IV neutropenia. The overall response included partial responses (PR) 18%, no change (NC) 55%, progressive disease (PR) 11% and the median survival from the start of outpatient chemotherapy was 384 days. The monthly average cost of medical care per inpatient was more than three times as high as that of outpatients. Cisplatin-free chemotherapy for advanced lung cancer should be given as outpatient treatment not only to maintain the quality of life of patients, but also to restrain the total cost of medical care and to use hospital beds efficiently.     

Rituximab and CHOP chemotherapy plus GM-CSF for previously untreated diffuse large B-cell lymphoma in the elderly: a Wisconsin oncology network study

PurposeHuman recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) may potentiate rituximab activity by upregulating CD20 expression and activating effector cells necessary for antibody-dependent cellular cytotoxicity. GM-CSF was combined with standard rituximab + CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy (R-CHOP) in the treatment of elderly patients with de novo diffuse large B-cell lymphoma (DLBCL).Patients and MethodsThirty-eight patients over the age of 60 years with newly diagnosed DLBCL were treated with R-CHOP every 21 days for 6–8 cycles and GM-CSF 250 μg/m² per day on days 3–10. Patients were evaluated for response after cycles 4, 6, and 8. The primary endpoint was the rate of complete response, and secondary endpoints were progression-free survival (PFS), event-free survival, and overall survival (OS).ResultsThirty-eight patients were enrolled, with a median age of 72 years, and 29% of patients having high-risk disease (International Prognostic Index [IPI] score ≥ 4). A complete or unconfirmed complete response (CR) was achieved in 53% of patients. After a median follow-up of 51.1 months, the 3-year PFS and OS were 78% and 84%. Twenty-one percent of patients discontinued protocol treatment because of chemotherapy-related toxicity and 16% because of GM-CSF toxicity. Dose intensity for planned chemotherapy cycles was 81.1%.ConclusionThese data suggest that survival outcomes may be modestly improved when GM-CSF is combined with R-CHOP in the treatment of elderly DLBCL. GM-CSF had toxicity precluding planned administration in 16% of patients, which may limit usefulness of this agent. Further investigation of GM-CSF in combination with rituximab-containing chemotherapy is warranted.     

Part II: Liver function in oncology: towards safer chemotherapy use

The liver is fundamentally important in drug metabolism. In oncology, the astute clinician must not only understand the meaning and limitations of commonly ordered liver biochemical tests, but also be aware of which anticancer agents might induce liver dysfunction, and of the strategies for appropriate dosing of patients with pre-existing liver dysfunction. In part I of our Review, we highlighted both the importance and inadequacies of identifying serum biochemical liver abnormalities in oncology; we also discussed a lack of routine formal investigation of liver function. We summarised chemotherapy-related hepatotoxicity and other causes of liver toxic effects in patients with cancer. Here in part II, we discuss trials that have specifically assessed chemotherapy dosing strategies in the setting of overt biochemical liver dysfunction and we note their recommendations. Furthermore, we review other assessments of liver metabolic and excretory function, particularly in the setting of chemotherapy drug handling. We discuss the potential use of these metabolic probes in practice.     

Outpatient chemotherapy of an advanced or metastatic colorectal cancer

We report the outpatient chemotherapy of an advanced or metastatic colorectal cancer. From April 2005 to May 2006, 50 patients were treated with FOLFIRI or FOLFOX in our hospital. Forty five patients (90%) had an intravenous catheter and a port for the chemotherapy, 23 patients (46%) were treated at the outpatient booths. We used the clinical pathway in chemotherapy for patients and co-medical roles. We were not experiencing emergency admission of side effects. Outpatient chemotherapy utilizing FOLFIRI or FOLFOX for advanced or metastatic colorectal cancer can be enforced safely by using the clinical pathway.     

Outpatient chemotherapy with infusional 5-fluorouracil in advanced gastrointestinal cancer

These studies were designed to evaluate the efficacy, toxicity, and resulting quality of life (QOL) of outpatient chemotherapy with infusional 5-FU for advanced gastrointestinal cancer. Schedule, sch. A: Treatment consisted of CI 5-FU 200 mg/m2/day, days 1-28, IVB Leucovorin 20 mg/m2 q week. Fifteen patients with advanced gastrointestinal cancer were treated to maintain the efficacy of prior inpatient chemotherapy. Twenty-one patients treated with adjuvant chemotherapy were added to evaluate toxicity and QOL. The mean time to progression (TTP) was 2.6 months. Grade 2 toxicities were seen, including mucositis (23%) and diarrhea (7%). Hand-foot syndrome was seen 60% of patients. The mean QOL score was 89.5 +/- 7.8. Sch.B: Treatment consisted of weekly 24 h infusion of 5-FU 2,600 mg/m2. 5-FU was administered using a Groshong catheter and Baxter infusor LV5 (5 ml/hr). Nine patients with advanced gastrointestinal cancer were treated. Twenty-one patients were treated with adjuvant chemotherapy. The mean TTP was 3.6 month. Grade 2 toxicities were seen, including leucocytopenia (7%), mucositis (3%), diarrhea (10%), and nausea and vomiting (10%). The mean QOL score was 82.6 +/- 10.7. In conclusion, both 5-FU schedules are feasible for outpatient chemotherapy for advanced gastrointestinal cancer.     

Outpatient management of acute promyelocytic leukemia after consolidation chemotherapy.

The feasibility and safety of outpatient management of acute promyelocytic leukemia (APL) during the aplastic phase after intensive consolidation chemotherapy, the incidence and types of complications requiring readmission to hospital, and the number of hospital days spared by this policy have been prospectively evaluated. After chemotherapy administration, patients were evaluated on an ambulatory basis. In the event of any complication they referred to the Emergency Unit (EU) of our Department dedicated to outpatients with hematologic diseases. Forty patients with APL observed over a 4 year period were eligible for intensive chemotherapy. After the achievement of complete remission they received a total of 104 consolidation courses and in 98 instances they were followed on an ambulatory basis. There were 41 cases (42%) of rehospitalization for fever (40 cases) or severe anemia (one case). Only one patient died due to a brain hemorrhage. Streptococcus viridans was the organism most frequently isolated from blood. Empiric once-a-day antibacterial therapy with ceftriaxone and amikacin was effective in 87% of the cases and made possible early discharge in 28% of the cases to continue the antibiotic therapy on an outpatient setting. Patients were managed out of the hospital for 76% of the post-consolidation neutropenia period. Thanks to the availability of an EU specifically dedicated to outpatients with hematologic diseases, out-hospital management of APL patients after consolidation therapy appeared to be safe, well accepted, potentially cost-saving, and contributed to saving the risk of developing severe nosocomial infections.     

Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer

This phase II study was conducted to determine the efficacy and toxicity of a gemcitabine (GEM) and oxaliplatin (OX) chemotherapy protocol in patients with unresectable biliary tract cancer (BTC). Patients were treated with GEM 1000 mg m-2 (30 min infusion) on days 1, 8, 15, and OX 100 mg m-2 (2 h infusion) on days 1 and 15 (gemcitabine and oxaliplatin (GEMOX-3 protocol), repeated every 28 days. The data were collected according to the Simon 2-stage design for a single centre phase II study (alpha=0.05; beta=0.2). Primary end point was response rate; secondary end points were time-to-progression (TTP), median survival, and safety profile. Thirty-one patients were enrolled in the study between July 2002 and April 2005. Therapeutic responses were as follows: partial response in eight patients (26%, 95% confidence interval (CI) 14-44), stable disease in 14 patients (45%, 95%CI 29-62), resulting in a disease control rate of 71%. Nine patients (29%, 95%CI 16-47) had progressive disease. Median TTP was 6.5 months. Median overall survival was 11 months. Common Toxicity Criteria (CTC) Grade 3-4 toxicities were transient thrombocytopenia (23%), peripheral sensory neuropathy (19%), leucopenia (16%), and anaemia (10%). In conclusion the GEMOX-3 protocol is active and well tolerated in patients with advanced BTC. It can be applied in an outpatient setting with three visits per month only.     

Outpatient chemotherapy plus radiotherapy in sarcomas: improving cancer control with radiosensitizing agents.

BACKGROUND: Cancer control by radiotherapy (RT) can be improved with concurrent chemotherapy. Outpatient strategies for sarcomas that combine chemotherapy and RT are possible since supportive care and RT techniques have improved. METHODS: The current status of non-anthracycline chemotherapy in combination with radiation for high-risk sarcoma is reviewed. RESULTS: Ifosfamide with mesna and newer activated ifosfamide agents (ZIO-201 and glufosfamide) have high potential to improve sarcoma cancer control. In Ewing's sarcoma and osteosarcoma, high-dose ifosfamide with mesna (2.8 g/m2/day of each x 5 days; mesna day 6) can be safely given to outpatients using continuous infusion. Reducing ifosfamide nephrotoxicity and central nervous system side effects are discussed. Other outpatient radiosensitization regimens include gemcitabine (600-1000 mg/m2/dose IV over 1 hour weekly x 2-3 doses), temozolomide (75 mg/m2/daily x 3-6 weeks), or temozolomide (100 mg/m2/dose daily x 5) + irinotecan (10 mg/m2/dose daily x 5 x 2 weeks). In osteosarcoma with osteoblastic metastases on bone scan, samarium (1 mCi/kg; day 3 of RT) and gemcitabine (600 mg/m2 IV over 1 hour day 9 of RT) is a radiosensitization strategy. Future drugs for radiosensitization include beta-D-glucose targeted activated ifosfamide (glufosfamide) and sapacitabine, an oral nucleoside with in vitro activity against solid tumors including sarcomas. CONCLUSIONS: The potential to treat major causes of sarcoma treatment failure (local recurrence and distant metastases) with concurrent chemotherapy during radiation should be considered in high-grade sarcomas.