Combined therapy for stage III-IV head and neck cancer: preliminary results.

As part of a combined modality treatment program using chemotherapy, surgery, and/or radiotherapy, 25 patients with previously untreated stage III or IV head and neck cancer received initial combination chemotherapy. Pathologically confirmed complete remission was noted in nine patients (36%). The overall objective major response rate (with all patients included in analysis) was 68%. The chemotherapy regimen included bleomycin, cisplatin, vinblastine, methotrexate, and 5-fluorouracil. A novel concept of drug scheduling was used, based on chemotherapy-induced improvement in RBC deformability. The underlying concept is that improved RBC deformability results in improved capillary blood flow and thereby, increased drug delivery to tumor cells. Treatment resulted in moderate hematologic and renal toxicity with no treatment-related deaths. This exceptionally high, pathologically confirmed complete response rate will hopefully provide a mechanism by which combined modality therapy can adequately be tested for its ability to prolong survival of patients with advanced head and neck cancer.

Septicemic complications of the cutaneous T-cell lymphomas.

The records of 60 consecutive patients with cutaneous T-cell lymphomas were reviewed to determine the incidence, etiology, predisposing factors, therapy, complications and outcome of septicemia. Fourteen (23 percent) patients had 26 septicemias: due to gram-positive cocci in 21 and to gram-negative bacilli in five. The presence of stage IV lymphomatous disease (p 0.032), generalized erythroderma (p less than 0.001), palpable lymph nodes (p 0.014), and histologic involvement of lymph nodes (p 0.023) and peripheral blood (p less than 0.001) identified a subset of patients at high risk for sepsis. Sepsis was correlated with locally infected sites in 77 percent of the episodes. Single antimicrobial therapy was successful in all septicemias due to gram-positive cocci but was accompanied by five secondary gram-negative bacillary superinfections (80 percent fatal). The subsequent mortality in all patients who survived infection (50 percent) indicated their poor over-all prognosis.

Safety and efficacy of continuous intravenous morphine for severe cancer pain.

To study the efficacy and safety of continuously administered intravenous morphine for cancer pain unrelieved by standard narcotic therapy, bolus intravenous injections of 2 to 5 mg of morphine were given every 10 minutes until pain relief was achieved. Within the next hour, continuous intravenous morphine infusion was begun with the hourly dose equal to the cumulative bolus dose. Respiratory rate, pulse, blood pressure, arterial blood gas values, mental status, and pain relief were recorded at baseline and during the study period. A reduction in arterial oxygen pressure (PaO2) and/or increase in arterial carbon dioxide pressure PaCO2 of more than 20 percent of baseline values occurred, during the first 24 hours of infusion, in a minority of patients. This did not require changes in hourly morphine dose. Despite subsequent increases in morphine dose, blood gas values tended to remain at or return toward baseline values. Severe toxicity occurred during one trial and was heralded by bradypnea and marked somnolence. Major pain relief was achieved in 11 of 15 trials. Therefore, continuous intravenous morphine is effective and safe therapy. Bradypnea associated with marked somnolence is a cause for dose reduction.

Herpes zoster and small cell bronchogenic carcinoma.

In nine of 74 (12 per cent) consecutive, previously untreated patients with small cell bronchogenic carcinoma receiving combination chemotherapy herpes zoster developed. This is the highest frequenzy reported for this viral infection in patients with nonlymphoproliferative solid tumors. Cutaneous dissemination developed in six of the nine patients, but visceral involvement did not occur. The major difference between the patients with herpes zoster and those without was the superior duration of median survival for the infected patients. No relationship could be established between the development of herpes zoster and the extent of neoplastic disease, prior radiotherapy, treatment with specific chemotherapeutic agents or corticosteroids, cutaneous anergy or granulocytopenia. Serum specimens obtained from six of the nine patients prior to their infection demonstrated the preexistence of varicella zoster antibodies. As more effective and intensive chemotherapy prolongs the survival of patients with solid tumors, it is possible that the frequency of herpes zoster infection may approach that observed in patients with lymphoproliferative malignancies.

Pneumocystis carinii pneumonitis in patients with lung cancer.

Pneumocystis carinii pneumonia was histologically documented in five patients with bronchogenic carcinoma. All patients had been treated with combination antineoplastic chemotherapy. Two patients received no corticosteroids, two received no chest radiotherapy, and one received neither radiotherapy nor corticosteroids. This suggests that as more patients with lung cancer are treated with intensive chemotherapy, pulmonary infection with P carinii may become an important differential diagnostic consideration in the presence of pulmonary infiltrates.

Fiberoptic bronchoscopy and culture bacteria from the lower respiratory.

Forty-five specimens were obtained by sequential translaryngeal aspiration and fiberoptic bronchoscopy from 31 clinically unifected patients with lung cancer in order to evaluate the reliability of routine fiberoptic bronchoscopy for culture of the lower respiratory tract. Bacteria were recovered brom 98 percent (44) of the specimens obtained via fiberoptic bronchoscopy and from 58 percent (26) of the specimens obtained by the preceding translaryngeal aspiration. The microorganisms grown from cultures of specimens obtained by fiberoptic bronchoscopy consisted of mixtures of both nonpathogenic and potenitally pathogenic bacteria. Potentially pathogenic bacteria were present in 87 percent (39) of the specimens from fiberoptic bronchoscopy and 31 percent (14) of specimens from translayngeal aspiration. The results of cultures from the two procedures agreed completely in only a single instance. Culture of washings or secretions obtained by routine fiberoptic bronchoscopy is not recommended because it provides inaccurate and clinically confusing information about the presence or types of bacteria in the lower respiratory tract prior to instrumentation.

Intravenous followed by oral antimicrobial therapy for staphylococcal endocarditis.

We have treated 35 cases of staphylococcal endocarditis in 33 patients with intravenous followed by oral antimicrobial therapy. All patients had three or more blood cultures positive for Staphylococcus aureus, and all had cardiac murmurs characteristic of valvular insufficiency. The mean total duration of antimicrobial therapy was 42.4 d, consisting of a mean of 16.4 d of intravenous therapy followed by a mean of 26 d of oral therapy. Intravenous antimicrobial therapy included sodium nafcillin (32 cases; mean dose 9.2 g daily) and clindamycin (three cases). Oral therapy included dicloxacillin or oxacillin (30 cases; mean dose 4.5 g daily), clindamycin (four cases), and potassium penicillin V (one case). Serum bactericidal titers using the blood culture isolates showed similar activity with both intravenous and oral drugs. All patients treated with this sequential intravenous and oral regimen were cured. A regimen of initial intravenous followed by oral antimicrobial therapy, monitored with serum antibacterial activity studies, is a safe, effective, well-tolerated, and economical treatment for staphylococcal endocarditis.

Staphylococcal bacteremia in cancer patients: intravenous and oral antimicrobial therapy.

Eighteen adult cancer patients with 21 episodes of staphylococcal bacteremia were treated with sequential intravenous and oral antimicrobial agents. Adequacy of antimicrobial therapy was monitored with serum antibacterial activity studies. The mean duration of intravenous and oral therapy was nine and 25 days, respectively. Clinical and bacteriologic cures were achieved in all cases except one, in which relapse occurred after only 16 days of therapy. One patient had staphylococcal endocarditis and one had staphylococcal pneumonia. Four patients died of causes unrelated to staphylococcal bacteremia after 12, 21, 27, and 40 days of therapy, respectively. Initial intravenous therapy followed by oral antimicrobial agents to complete treatment, monitored with serum antibacterial activity studies, is effective therapy for patients with cancer and staphylococcal bacteremia.

Counterimmunoelectrophoresis of staphylococcal antibody.

Modifications of the staphylococcal counterimmunoelectrophoresis technique were evaluated to determine how variations in the procedure affected results. Neither a buffer pH range of 7.8 to 9.0 nor buffer molarity of 0.015 or 0.025 when tested in combinations caused appreciable differences. However, use of different agar preparations or delay in addition of antigen to the test slide altered the location of the precipitin band. Agarose was found to be more sensitive in determining the serum precipitin titer and provided a better photographic record than either Ionagar or Noble agar.

Pseudomonas endocarditis: cure with carbenicillin and polymyxin B.

A case of Pseudomonas endocarditis cured with carbenicillin and polymyxin B is described. Initially, this patient was considered a medical treatment failure when a full course of carbenicillin and gentamicin failed to effect a cure. The importance of monitoring therapy with appropriate laboratory tests is stressed.

Treatment of localized pulmonary phycomycosis.

A patient cured of localized pulmonary phycomycosis occurring at the site of a previous lung abscess is described and the other survivors of this unusual entity are discussed. Whole-lung computerized tomographic (CT) scanning was useful in confirming the presence of a single localized lesion and led to the choice of surgical excision. A diagnostic and therapeutic approach including whole-lung CT scanning and preoperative and postoperative systemic amphotericin B therapy is suggested pending pathologic review of the tissues for possible fungal invasion beyond the resected area. The value of surgical excision when the disease appears localized is emphasized.

Nafcillin entry into human cerebrospinal fluid.

The entry of nafcillin into the cerebrospinal fluid (CSF) of humans was studied in the absence of meningeal inflammation. Twenty studies were performed in 18 patients receiving 40 mg of sodium nafcillin per kg intravenously over 30 min. The CSF specimens were obtained at 1, 2, 3, and 4 h postinfusion, and sera were obtained at 5 min and 1, 2, 3, and 4 h. Nafcillin was uniformly detected in the lumbar CSF at 1 h, peaked at 2 h postinfusion, and was still detectable in the CSF of three of four patients studied at 4 h.

Bacteremia due to Staphylococcus aureus in patients with cancer: report on 45 cases in adults and review of the literature.

The frequency, predisposing factors, therapy, and outcome of 45 episodes of bacteremia due to Staphylococcus aureus were reviewed in adult cancer patients. A poor performance status (i.e., patients largely bedridden), progressive neoplastic disease, and compromise of the mucocutaneous defense barriers characterized the patients with S. aureus sepsis. Seventeen patients died soon after the onset of infection: seven (16%) as direct result of staphylococcal sepsis, seven of factors unrelated to infection, and three of secondary sepsis due to gram-negative bacilli. The data presented here and reported by others indicated that (1) the incidence of staphylococcal sepsis in cancer patients has recently increased from a low point of 5% to a level as high as 30%; (2) breaches in the epithelium are the most important factors determining risk; (3) there are three effective approaches to therapy depending upon the clinical setting; and (4) the outcome appears to be determined by the status of the neoplastic disease and by early institution of appropriate antimicrobial therapy.

Absence of bacteremia after fiberoptic bronchoscopy.

Fiberoptic bronchoscopy was performed in 43 consecutive afebrile patients with lung cancer. Blood cultures were drawn before the procedure, immediately afterward, and 30 min later. Although bacteria were isolated from all bronchoscopic washings and the majority of translaryngeal aspirates cultured, all blood cultures were bacteriologically sterile. No fever or evidence of infection developed in any patient within 24 hours after the procedure.

Perirectal infections in patients with small cell lung cancer.

Fifteen anorectal infections occurred in 6.4% of 188 intensively treated patients with small cell bronchogenic carcinoma. Granulocytopenia was present at onset in 13 episodes. In eight episodes, perirectal pain preceded any objective findings by two to 11 days. Ten infections resolved with recovery from granulocytopenia, but the five abscesses required incision. Septicemia accompanied four episodes; one patient died. Early recognition and therapy of this potentially fatal infection will become increasingly important as more patients with solid tumors receive intensive therapy.

An active chemotherapy regimen for squamous cell lung cancer.

A new concept of chemotherapy scheduling was evaluated in 20 patients with inoperable squamous cell lung cancer. The complete plus partial response rate was 85%, with 15% complete responses. The drugs utilized included vinblastine, bleomycin, methotrexate, 5-FU, cisplatin, and leucovorin. The hypothesis leading to the chosen drug schedule was that impaired rbc deformability (RBCD) found in cancer patients may produce stasis of flow in tumor capillary beds and decrease drug delivery to cancer cells. Drug schedules were designed to take advantage of chemotherapy-induced improvement in RBCD. After an initial drug treatment, a second treatment was given when RBCD increased at least 25% over pretreatment values (usually 4-6 days after the first chemotherapy dose). Drug doses were weighted so that more drug was given when RBCD was greatest. Treatment toxicity was predominantly hematopoietic and renal. This type of chemotherapy approach opens up new avenues of investigation in squamous cell cancer and other common neoplasms.

Superior vena cava syndrome due to non--small-cell lung cancer. Resolution with chemotherapy alone.

Three patients with superior vena cava syndrome due to non--small-cell lung cancer were treated with chemotherapy alone. Symptomatic relief began within three days of treatment and substantial resolution of the syndrome occurred in all three patients. One patient had complete remission of tumor and the other two had more than a 50% tumor reduction within the first month of therapy. These are the first case reports indicating that combination chemotherapy may be effective as initial management of the superior vena cava syndrome due to non--small-cell lung cancer.