Schedules concurrent

Unanswered questions with the use of adjuvant trastuzumab include optimal concurrent chemotherapy, optimal dose, schedule and duration of therapy, and use of other concurrent therapeutic modalities. 

Closed meeting for report development. Complete concurrence draft for EDS I Pueblo report and preconcurrence draft for Demo II report. Schedule next meeting date and discuss items for the agenda. 

The protocol should specify what should be recorded directly into the CRF and what will also be recorded in the medical records. The CRF will contain all the pertinent data associated specifically with the clinical trial but some will be repeated in the medical records, for example, the protocol identification number, date of consent, date of commencement of the study, key baseline medical findings, visit dates, start and finish dates of the study drug/placebo or treatment, concurrent medication, adverse events and key efficacy and any unscheduled or scheduled actions or interventions (such as escape medication). Additional information obtained from biopsy reports, radiographs and similar documents will provide confirmation that the data in the CRF are recorded correctly. Monitors, QA auditors and inspectors need to see all the medical records available to the investigator. It is not appropriate to create copies of data from CRFs or checklists derived from medical records and claim that these are source documents. 

Fig. 7. A schematic representation of treatment of 5-FU and external irradiation. The stippled rectangles represent weekly irradiation (9 Gy total/wk, given in five doses of 1.8 Gy). Concurrent 5-FU is represented by the solid bars beneath the irradiation, and the height of the bars represents the peak level of radiosensitizing chemotherapy. By using protracted infusional schedules of 5-FU, radiosensitizing chemotherapy can be given with each daily dose of irradiation (from 5 to 3 5 d). Newer schedules using continuous intermittent and circadian schedules have achieved high tumor activity with acceptable toxicity in recent trials.

Prior clinical trials have attempted to discern the best manner in which to administer chemotherapy when combined with radiation. It may be given concurrently with standard radiotherapy, an alternating or split-course radiotherapy schedule, or in a sequential fashion as induction (prior to definitive treatment) or adjuvant (following definitive treatment) chemotherapy. Concomitant chemoradiotherapy is the use of both modalities simultaneously. Alternating chemoradiotherapy is the use of systemic chemotherapy for a definitive duration, followed by radiotherapy for a specified period followed by repeated alternations of the two modalities. Split-course chemoradio-therapy usually involves concomitant systemic doses of chemotherapy combined with radiation therapy for a specified duration followed by a rest period, and then the regimen is repeated. This approach allows planned treatment breaks for toxicity recovery. 

The optimal timing and sequence of combining chemotherapy and radiation therapy is unknown for the treatment of limited-stage small-cell lung cancer. Radiation can be combined with chemotherapy sequentially, alternating, or concurrently. When combined concurrently, radiation can be started early in the treatment or later during the treatment schedule. 

Concurrent schedule of chemotherapy and radiation therapy is defined as the delivery of radiation and chemotherapy simultaneously either early or late in the treatment schedule. The advantage of this schedule is that by giving the radiation and chemotherapy together early in the treatment course one can possibly prevent the development of resistant tumor cells. However, the disadvantages include increased toxicides and the decreased ability to deliver full dose chemotherapy (36). 

A Japanese trial compared sequential delivery of chemotherapy and radiation therapy to concurrent delivery of chemotherapy and radiation (47). Patients were randomized to receive concurrent hyperfractionated radiation therapy (d 2 of cycle 1 of chemotherapy) or to sequential chemotherapy followed after the fourth cycle by hyperfractionated radiation therapy. The radiation dose was45 Gygivenin 1.5 Gy fractions twice daily for a total of 30 fractions in 3 wk. The chemotherapy given was cisplatin and etoposide. The median survival for the concurrent schedule was 29 mo and for the sequential schedule was 19 mo. The 2-yr survival was 50% for the concurrent therapy and 40% for the sequential therapy (47). These results favored concurrent therapy and are the best results to date for patients with LD-SCLC. 

Other studies evaluated the question of whether early delivery of radiation concurrently with chemotherapy was better than late delivery. A study performed by the C ALGB randomized patients to early (d 1, cycle 1), late (d 64, cycle 4), or no radiation therapy. The radiation therapy dose was 50 Gy over 6 wk. Chemotherapy used in this trial was cyclophosphamide, etoposide, and vincristine. The local recurrence rate for the early, late, and no radiation therapy arms was 49%, 68%, and 82%, respectively. The 2-yr progression-free survival rate was 15% for the early schedule arm vs 25% for the late schedule (p = 0.078). The 5-yr survival rate for the early, late, and no radiation therapy arms was 6.6%, 12%, and 3%, respectively (p = 0.007). The poor 5-yr survival rate for the early schedule was felt to be due to the significant decrease in chemotherapy dose needed for the early schedule group (4,49). 

Choi NC, Herndon JEII, Rosenman J, et al. Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer. J Clin Oncol 1998 16 3528-3536. 

In fact, with more moderate-to-severe episodes, a mood stabilizer alone is usually insufficient, and initial treatment often requires a concurrent antipsychotic, preferably a novel agent. In these situations, we advocate using an initial lower-dose schedule (e.g., risperidone 1 to 4 mg/day olanzapine 2.5 to 10 mg/day). If primary mood stabilizers are ineffective or not tolerated, evidence indicates that monotherapy with agents such as olanzapine or risperidone may be effective. 

Two decades ago, Richard Hermstein (1961) proposed his matching law, a formula which summarized the choices animals made on concurrent variable interval schedules. This formula was parsimonious in the extreme, containing no empirical constants ... 

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