Interfraction interval does not affect survival of patients with non-small cell lung cancer treated with chemotherapy and/or hyperfractionated radiotherapy: a multivariate analysis of 1076 RTOG patients.

PURPOSE: It was observed by Jeremic et al. that a shorter interfraction interval (IFI) was associated with an improved survival in patients (pts) with locally advanced non-small cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (HFX-RT), with or without chemotherapy (CT). Our analysis was undertaken to verify this hypothesis. METHODS AND MATERIALS: Records of patients treated on 5 Radiation Therapy Oncology Group (RTOG) studies were reviewed, and an actual IFI, defined as a mean of all daily IFIs, was calculated. RT dose was 1.2 Gy BID to 69.6 Gy. The relationship between the length of IFI and the median survival time and incidence of esophagitis was investigated. RESULTS: In 682 pts eligible for this analysis, a full dose of RT was delivered and at least 90% of all daily IFIs were available. The actual mean IFI was as follows: 4-4.9 h in 51% of pts; 5-5.9 h in 17%; 6-6.9 h in 28% and 7-8 h in 4%. In multivariate analysis, only lack of weight loss, use of CT, low nodal stage and good KPS, but not IFI (4-6 h vs. 6-8 h) were associated with an improved survival for all pts (p values: <0.0001; <0.0001; 0.006; 0.006, and 0.73, respectively), as well as for HFX-RT only pts. For the CT-HFX-RT pts, not enough data points are available for a meaningful analysis. Length of IFI did not influence the incidence of Grade 3 or higher esophagitis (p = 0.82), but use of CT was associated with a 12-fold greater risk of developing severe esophagitis (p < 0.0001). CONCLUSION: Length of IFI (4-6 h vs. 6-8 h) did not influence survival and acute complications incidence in pts with NSCLC treated in RTOG studies with HFX-RT to 69.6 Gy. Previously identified factors, such as use of CT, minimal weight loss, good KPS and low nodal stage, were confirmed again to be associated with a favorable prognosis in a multivariate analysis. Use of CT was associated with a 12-fold greater risk of developing severe esophagitis than HFX-RT alone. It appears that an IFI of 4-8 hr is acceptable in clinical practice for pts with NSCLC, treated with HFX-RT.

Impact of adding concurrent chemotherapy to hyperfractionated radiotherapy for locally advanced non-small cell lung cancer (NSCLC): comparison of RTOG 83-11 and RTOG 91-06.

A hyperfractionated radiation therapy (HFX RT) trial (1.2 Gy twice daily, b.i.d.) (HFX) for non-small cell lung cancer (NSCLC) showed that 69.6 Gy resulted in better survival than did lower total doses (Radiation Therapy Oncology Group, RTOG 83-11) and that cisplatin concurrent with irradiation improved local control and survival over RT alone (Radiation Therapy Oncology Group, RTOG 91-06). Concurrent combination chemotherapy and HFX could improve both local and systemic control. In a phase II trial (RTOG 91-06) for inoperable NSCLC, two cycles of PE were used [cisplatin 50 mg/m2 intravenously (i.v.) days 1 and 8, etoposide 50 mg orally (p.o.) b.i.d., 75 mg/day if body surface area (BSA) < 1.7 m2, days 1-14] starting on day 1 of HFX (69.6 Gy) and repeated on day 29. HFX/PE was compared with HFX (69.6 Gy) from an earlier phase II trial (RTOG 83-11). Seventy-six patients treated with HFX/PE and 203 patients who received HFX alone were compared for toxicity, response, survival, and patterns of failure. The rates of grade 4 nonhematologic toxicity were similar (3.0% for HFX/PE, 3.0% for HFX), but grade 4 hematologic toxicity occurred only with HFX/PE 56.6%. Three (3.9%) HFX/PE patients had fatal toxicity (2 pulmonary, 1 renal); 1 HFX patient had fatal esophageal toxicity. Response and metastasis rates were similar for the two treatments, but infield (p = 0.054) and overall (p = 0.04) progression-free survival rates were better with HFX/PE. Median survivals were 18.9 months with HFX/PE and 10.6 months with HFX. Two-year survival rates were 36% for HFX/PE and 22% for HFX (p = 0.014). The differences in survival between HFX/PE and HFX remained borderline statistically significant (p = 0.0593) in the multivariate model, which included weight loss, Karnofsky performance status (KPS), sex, and stage. HFX/PE is an effective regimen in patients with inoperable NSCLC, although it is considerably more toxic, and is undergoing a comparison in a three-arm randomized phase III study against induction cisplatin/vinblastine plus standard once-daily RT and against cisplatin/vinblastine concurrent with standard RT.

Flutamide-associated liver toxicity during treatment with total androgen suppression and radiation therapy for prostate cancer.

PURPOSE: To examine the frequency and severity of toxicity associated with flutamide inpatients treated with total androgen suppression before and during pelvic radiation therapy (RT) for prostate cancer. MATERIALS AND METHODS: Sixty-five patients with T2b-T4 prostate cancer received flutamide and goserelin acetate for 4 months, with RT beginning at the 3rd month. Treatment records including liver function test (LFT) results at baseline and during treatment were reviewed and toxicities noted. RESULTS: In 30 (46%) of 65 patients, flutamide was discontinued prematurely. Primary reasons included elevation in LFT levels (n=14); gastro-intestinal toxicity (n=9); decreased hemoglobin level (n=2); patient refusal (n=2); and arthralgia, rash, and malaise (n=1 each). Hepatotoxicity generally was manifest as asymptomatic transaminase level elevation. Grade 3-4 hepatotoxicity was noted in four of 65 patients. Mean aspartase aminotransferase increased from 23 (baseline) to 67 U/L (during flutamide treatment) (P<.02); mean alanine aminotransferase level increased from 26 (baseline) to 94 U/L (during flutamide treatment) (P<.005). CONCLUSION: Flutamide toxicity was common. LFTs should be monitored during flutamide therapy. The role of flutamide in this treatment regimen may need to be reevaluated.

Analysis of sites and causes of failures of irradiation in invasive squamous cell carcinoma of the intact uterine cervix.

An analysis of the records of 916 patients who received radiotherapy for invasive squamous cell carcinoma of the intact uterine cervix from January 1964 through December 1969 revealed that 94% of the central and regional failures will occur within 3 years of treatment. Survival rates were as follows: Stage I, 91%; Stage IIA, 82%; Stage IIB, 65%; Stage IIIA, 54%; and Stage IIIB, 40%. The incidences of central and regional failures in Stages I through III are: Stages I and IIA; central 2% and regional 4.5%; Stage IIB; central 5% and regional 13%; Stage III: central 14% and regional 19%. In stages IIB, IIIA, and IIIB, the main cause of failures, either centrally or in the parametria, is the presence of massive disease.