The calculation of actual or received dose intensity: a comparison of published methods.

Abstract

Two recent reports of the same combination chemotherapy program, cyclophosphamide, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, bleomycin, and prednisone (ProMACE-CytaBOM), in similar subsets of patients with advanced-stage aggressive-histology lymphoma used two different methods to report the actual dose-intensity (DI) data. One method treats DI as a property of a particular cycle of treatment within the entire population that received that cycle. The other treats DI as a characteristic of a particular patient's entire treatment course. We have applied both methods to the same set of data and provide evidence that the latter method is preferable for at least two reasons: (1) it more accurately reflects actual DI by clearly incorporating the duration of the actual treatment course and, thus, can be used to compare the administration of same or related regimens to distinct patient populations; and (2) it allows assignment of a numerical value to an individual patient's treatment course or a group of patients' treatment courses such that DI can be examined for its impact on treatment outcome just like any other prognostic factor. The observed differences in treatment outcome between the Southwest Oncology Group (SWOG) and National Cancer Institute (NCI) studies are not clearly related to differences in distribution of clinical prognostic factors in the two study populations. The differences in methods of reporting DI prohibit evaluation of the influence of dose-related variables on outcome in the two studies. Adoption of a standard method of calculating and reporting DI data would facilitate evaluation of the prognostic significance of DI.

Efficacy and feasibility of standard procarbazine, lomustine, and vincristine chemotherapy in anaplastic oligodendroglioma and oligoastrocytoma recurrent after radiotherapy

“…13,14 However, 43% of patients without disease progression discontinued therapy because of incomplete recovery from toxicity. The persistent toxicity determines a decrease in the relative dose intensity of PCV calculated according to the method of Longo et al 16 The relative dose intensity began to decrease at Cycle 3, and at Cycle 6, Ͻ 20% of the relative dose intensity was administered (Fig. 1).…”

“…The question of whether it is more useful to use temozolomide or PCV as the first-line chemotherapy is widely debated because the latter most likely has a greater activity, but also a greater toxicity, which is sometimes persistent, FIGURE 1. Relative dose intensity of lomustine and procarbazine calculated according to Longo et al 16 for patients with nonprogressing oligodendroglioma receiving the procarbazine, lomustine, and vincristine regimen. PCZ: procarbazine.…”

Impact of Chemotherapeutic Dose Intensity and Hematologic Toxicity on First Remission Duration in Dogs with Lymphoma Treated with a Chemoradiotherapy Protocol

“…29 To quantify dose intensity, several mathematical models have been used; the most common approach involves determining summation dose intensity (SDI). 30,31 These methods allow comparison of intended dose intensities for different protocols and comparison of received dose intensities among individual patients. Such mathematical approaches involve many assumptions that may be difficult to validate, including equivalent efficacy for each drug, a linear drug dose-response relationship, and a lack of synergistic or antagonistic interactions among drugs.…”

Salvage treatment in male patients with germ cell tumours

“…mg m 2, Cisplatin 100 mg mr-2) (Table II). Seven patients primarily received high dose Cisplatin schedules (BEP40/60) (Cisplatin 180 mg-200 mg m-2) (Longo et al, 1991).…”