Enrique Velez-Garcia

Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer.

PURPOSE To determine the cardioprotective effect of dexrazoxane (DZR) used in a doxorubicin-based combination therapy in advanced breast cancer. PATIENTS AND METHODS Between November 1988 and January 1991, 534 patients with advanced breast cancer were randomized to two multicenter, double-blind studies (088001 and 088006). Patients received fluorouracil, doxorubicin, and cyclophosphamide (FAC) with either DZR (DZR-to-doxorubicin ratio, 10:1) or placebo (PLA) every 3 weeks and were monitored with serial multiplegated acquisition (MUGA) scans. RESULTS The hazards ratio (HR) of PLA to DZR for a cardiac event, which was predefined ejection fraction changes or congestive heart failure (CHF), was 2.63 (95% confidence interval [CI], 1.61 to 4.27; P < .001) for 088001 and 2.00 (95% CI, 1.01 to 3.96; P = .038) for 088006. The objective response rates for 088001 were 46.8% for DZR and 60.5% for PLA, a difference of 14% (95% CI, -25% to -2%; P = .019), and for 088006 were 53.7% for DZR and 49.3% for PLA, a difference of 4% (95% CI, -13% to 22%; P = .63). Time to progression and survival were not significantly different between treatment arms in either study. Toxicities on the DZR arms included lower granulocyte and platelet counts at nadir (P = .009 and P = .004, respectively) and more pain on injection (P = .001), with no difference in the rates of fever, infection, or hemorrhage. CONCLUSION DZR had a significant cardioprotective effect as measured by noninvasive testing and clinical CHF. One of the two studies (088001) showed a lower response rate with DZR, but time to progression and survival were not significantly different. DZR is the first agent shown to reduce cardiotoxicity from doxorubicin.

Hyperinfection syndrome with Strongyloides stercoralis.

Abstract Infection with the parasitic nematode,Strongyloides stercoralis, can lead to death in patients with various clinical disorders. Alteration of the parasite—host relationship may lead to hyp...

Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes : a South-Eastern cancer study group (SEG) trial

In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.

The adjuvant treatment of inoperable stage III and IV epidermoid carcinoma of the head and neck with platinum and bleomycin infusions prior to definitive radiotherapy: An RTOG pilot study

Twenty‐nine previously untreated patients with advanced unresectable Stage III or IV epidermoid carcinoma of the oral cavity, oropharynx, hypopharynx, or nasopharynx were entered on a pilot protocol to evaluate the effectiveness and toxicity of platinum‐bleomycin infusion chemotherapy administered prior to definitive radiotherapy. Platinum was given by 24‐hour continuous I.V. infusion (in an attempt to decrease gastrointestinal and renal toxicity) without mannitol diuresis at a dose of 80–100 mg/m2 on day 1 and repeated on day 22. Bleomycin was administered 15 U/m2 I.V. push on day 3 and was then followed by a five‐day continuous I.V. infusion of 15 U/m2/day. Fourteen of 29 (48%) patients achieved an objective partial response on chemotherapy alone (an additional 5 patients or 17% had a minor response). Chemotherapy was well tolerated with 10/29 experiencing no nausea, 4/29 mild nausea alone, and 14/29 experiencing controllable nausea/vomiting. Transient reversible azotemia was noted in 4, skin rash in 3, and anemia in 9 patients. All 29 patients began radiotherapy on day 28; 25 completed radiotherapy and 12/25 (48%) achieved complete tumor clearance; all 12 are currently free of disease with short follow‐up. The radiotherapy was well tolerated, completed on schedule, and no unexpected toxicities were encountered. This combined modality approach demonstrated substantial antitumor activity and was able to reduce the significant morbidity from platinum‐bleomycin chemotherapy for the treatment of unresectable head and neck carcinoma.

Chemotherapy for head and neck cancer. Comparison of cisplatin + vinblastine + bleomycin versus methotrexate

One hundred ninety‐one patients with recurrent or metastatic squamous cell carcinoma of head and neck origin were allocated at random to chemotherapy with conventional‐dose weekly intravenous methotrexate or the combination of cisplatin, vinblastine, and bleomycin. Methotrexate induced responses in 16 of 98 patients (16%), whereas 22 of 92 (24%) responded to the combination regimen (P = not significant). Remission duration (20.2 weeks methotrexate; 15.1 weeks combination) was similar on both arms, as was survival (31.4 weeks methotrexate; 29.0 weeks combination). Therapy was relatively well‐tolerated on both treatment arms, although methotrexate produced more mucositis and the combination more gastrointestinal and renal toxicity. Response to chemotherapy and disease confined to the locoregional area were associated with somewhat longer survival. Combination chemotherapy as given in this study did not improve any observed parameter, and the results of treatment were poor in both arms.

BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease.

Three hundred twenty‐four evaluable patients with advanced or recurrent Hodgkins disease were treated with BVCPP. After stratification according to amount of prior therapy, patients who achieved complete remission were randomized to no additional therapy, 6 monthly cycles of MOPP or 6 additional monthly cycles of BVCPP. Complete remission rates were comparable to other studies: 68–73% for those who had not received prior chemotherapy and 28% for those who had. Although curves of disease‐free survival suggested that BVCPP maintenance therapy significantly prolonged a complete remission in previously untreated patients, multivariate analysis did not demonstrate such therapy to be a significant prognostic factor. Rather, favorable prognostic indicators were shown to be related to host factors. Subsequent analysis demonstrated that the maintenance and no‐maintenance groups of previously untreated patients were not strictly comparable in that the maintained group had more patients with favorable histologies who were less than 40 years of age. Herpes Varicella Zoster was not found to affect prognosis adversely. It is concluded that maintenance chemotherapy with BVCPP or MOPP does not significantly improve duration of complete remission or survival and that further comparative or sequential studies should include stratification of the important factors influencing duration of response and survival. Further, even though second remissions may be induced in the previously treated, their subsequent prognosis is poorer. For all patient groups female sex and an initial lymphocyte count > 1,372 were favorable factors. For those with little or no prior therapy, age <40, Caucasian race, and having lymphocyte predominance or nodular sclerosis favorably influenced the outcome as well. For those with major prior therapy not having had prior chemotherapy, having IIIA disease, and not having nodular sclerosis were important additional determinants of remission or survival. Cancer 42:2101–2110, 1978.

Results of a uniform histopathologic review system of lymphoma cases a ten‐year study from the southeastern cancer study group

To determine the usefulness of a consulting panel for histopathologic review in lymphoma cases, a comparative study of the histopathologic diagnosis of the local pathologist was done and compared with the final diagnosis by an expert pathologist in 1088 cases of lymphoma studied by the Southeastern Cancer Study Group (SECSG) during the implementation of five protocols during the last ten years. The following conclusions were reached: (1) In 44 cases (4%), the material sent for review was judged inadequate to make a diagnosis; (2) In 82 cases (8%), the local pathologists diagnosis was judged incorrect; (3) In Hodgkins Disease (HD), the diagnosis was confirmed in 545 of 595 cases (92%). However, using the Lukes and Butler classification by subtype of HD, the expert pathologist judged only 289 of 595 cases as correct (49%). The least agreement was found in the lymphocytic predominance (LP) subtype, in which only six of 34 (18%) cases were correct. The best correlation was found in the nodular sclerosis (NS) type of HD where agreement occurred in 161 of 186 (87%) cases; and (4) In the non‐Hodgkins lymphomas (NHL) the diagnosis was confirmed in 428 of the 493 cases studied (87%). Subclassification using the Rappaport system revealed agreement in 274 of 493 (56%) cases. Subtypes associated with good prognosis were judged correct by the expert pathologist in 105 of 139 instances (76%). Likewise, agreement in subtypes of poor prognosis occurred in 254 of 351 cases (72%). These data again confirm the need for an uniform consulting panel system especially for cases involved in cooperative group trials. This has even become more important now with the increasing complexity of the different classifications currently in use.

Multidrug chemotherapy (vincristine-bleomycin-methotrexate) followed by radiotherapy in inoperable carcinomas of the head and neck: Preliminary report of a pilot study of the radiation therapy oncology group

Abstract This is a preliminary report on the Radiation Therapy Oncology Group (RTOG) pilot study 77-08, of a combination of chemotherapy with vincristine-bleomycin-methotrexate, followed by radiotherapy, for inoperable carcinomas of the bead and neck. The main objectives of the study were to determine toxicity and tumor control. Patients who were included bad untreated carcinomas, with no distant metastases, and with adequate pulmonary, renal, and liver function. Forty patients were registered for the study. Chemotherapy started with vincristine—1.5 mgs/m 2 (maximum of 2 mgs) by I,V. injection, Wowed by bleomycin drip for 48 hours (15 units/day), and then methotrexate (200 mgs/m 2 divided in equal doses 6 hours apart) with folinic acid rescue. Eleven patients received one course of the stated chemotherapy; 28 were given two courses with one week rest period between them. Radical curative radiotherapy was started usually two weeks after chemotherapy. A surgical procedure was considered if the patient was found operable after receiving a dose of 5000 rad with continuous therapy or at 3000 rad with split-course therapy. The level of toxicity that resulted from this combined therapy was considered acceptable. The percentage of complete response of the primary tumor was 6% with chemotherapy; this increased to 46% after irradiation, and to 65% when surgery was added.

A phase II trial of CI-921 in advanced malignancies.

CI-921, (9-[[2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino]-N,5-dimethyl-4-acridinecarboxamide 2-hydroxyethanesulfonate (1∶1)), an anilinoacridine derivative with activity in experimental solid tumors was studied in a multicenter phase II trial in patients with solid tumors. Eligible tumor types included cancers of the breast, stomach, pancreas, nonsmall cell lung, small cell lung, colon, head and neck area, and melanoma. Prestudy requirements included an ECOG performance status of ≤ 2, no CNS metastases, and measurable disease. CI-921 was administered intravenously over 1–2 hours on days 1,8, and 15 of a 35-day course at an initial dose of 270 mg/M2, with modification in subsequent courses based upon tolerance. Principal toxicities included leukopenia, marked phlebitis, and mild nausea and vomiting. One hundred fifty patients were entered of whom 132 were evaluable for response. There was one complete and one partial response among 19 patients with breast cancer, and two partial responses, one each among 14 head and neck and 36 nonsmall cell lung cancer patients.

Postmastectomy adjuvant chemotherapy with or without radiation therapy in women with operable breast cancer and positive axillary lymph nodes: The Southeastern Cancer Study Group experience

SummaryBetween September 1976 and June 1982, 308 patients with operable breast cancer with 1–3 involved axillary nodes were stratified according to institution, type of mastectomy, and time from surgery to protocol entry, and then randomized to receive either six or 12 months of adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). With a median time of follow-up of 33 months, relapse rates among 181 reviewed and evaluable patients are 20/85 (23.5%) for pre- and 23/96 (24%) for postmenopausal patients. Results for premenopausal women, while better than historical controls at a similar time interval, appear inferior to other published adjuvant studies (e.g., NSABP and Milan). Although total relapse rates were 23/100 (23%) for six months and 20/81 (25%) for 12 months of therapy, suggestive differences were encountered by menopausal status with early trends favoring 12 months of treatment for premenopausal patients and six months of treatment for postmenopausal patients. During this same period, 283 patients with four or more involved axillary nodes were randomized to 1–3 treatment arms: six months of CMF, six months of CMF preceded by local-regional x-ray therapy (XRT), or 12 months of CMF. The latter arm was closed in February 1980 while the two six-month chemotherapy arms remain open as of January 1983. Relapse rates for 174 reviewed and evaluable patients on the three arms include: 27/76 (36%) for six months CMF, 15/54 (28%) for XRT and CMF, and 24/44 (45%) for 12 months CMF. Local-regional relapse rates were 12/120 (10%) for the combined two non-XRT arms and 3/54 (6%) for the XRT treatment arm (p = 0.34). Thus, at this early stage of follow-up there are still no statistically significant differences between six or 12 months of adjuvant CMF therapy and neither definite beneficial nor detrimental effects of prechemotherapy adjuvant radiation therapy. Longer follow-up will be needed to provide definitive conclusions.