Methods

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Using MEDLINE (1966 to October 1992), we searched the English-language medical literature (with the addition of reference 33 translated from Japanese) that describes the treatment of malignant pleural effusions. We found reports of 1168 patients who were treated with intrapleural agents for pleurodesis. The following information was extracted from each article: pleurodesis regimen, number of patients, success rate (complete response), and adverse effects. Because criteria for success varied, we defined success as complete response only: the absence of reaccumulation of the effusion determined by clinical examination or chest radiograph. Partial response criteria differed among trials and were not included in some reports. We did not compare response duration for the various treatment regimens because of variability and inconsistency in reporting.

Chemical Agents

Tetracycline Hydrochloride

Although it has not been approved by the Food and Drug Administration for pleurodesis, intrapleural administration of intravenous tetracycline (Achromycin, American Cyanamid; Pearl River, New York), with or without intrapleural lidocaine [13], gained acceptance in the last two decades as the pleurodesis agent of choice [4, 14]. It has been proven to be safe, effective, inexpensive, and easily administered, with reported adverse effects limited to pain (14%) and fever (10%) [3, 15] (Table 1). Intrapleural administration of the tetracyclines is usually in 30 to 50 mL of 0.9% saline, with an indwelling time of 2 to 6 hours. Its mechanism of action has been attributed to growth-factor-like activity on fibroblasts from both direct mesothelial cell activation [16] and indirect mesothelial cell activation through stimulated pleural macrophages [17].

Results of early studies [1, 18-25] using tetracycline in doses of 500 mg reported complete response in 52 (45%) of 115 patients. Subsequent studies [26-29], using doses of 1 g to 20 mg/kg body weight, reported response rates of 77%. Gravelyn and colleagues [25] treated 20 patients with 500 mg of intrapleural tetracycline and 12 patients with 1 g or more. A complete response was seen in only 5 (16%) of 32 patients, with 4 of the 5 patients receiving 1 g or more of tetracycline. Adverse effects did not differ according to dosage.

In a randomized trial in 50 patients with malignant pleural effusions, 25 patients received a single dose of tetracycline, 20 mg/kg, and 25 received two doses of 20 mg/kg on consecutive days [28]. No significant difference was found in complete response between single-dose (88%) and double-dose (96%) groups.

Doxycycline

Intrapleural doxycycline (Vibramycin, Pfizer; Groton, Connecticut) produced a complete response in 43 (72%) of 60 patients (see Table 1). However, only 6 [10%] patients had a complete response after a single 500-mg dose of doxycycline, 6 (10%) patients after two doses, 14 (23%) patients after three doses, and 6 (10%) patients after four doses. More than four doses were required for a complete response in the remaining 11 (18%) patients [30]. Pain was reported in 40% of patients and fever occurred in 7%.

Kitamura and colleagues [31] administered intrapleural doxycycline hyclate, 500 mg, to 15 patients with malignant pleural effusions twice weekly for 1 to 2 weeks. Complete response was seen in 10 (67%) patients, with a response duration of 2 to 10 months (average, 6.3 months). Mild chest pain, not requiring analgesics, was the only reported adverse effect and occurred in 5 (33%) patients.

Mansson [32] reported a complete response in 11 of 18 (61%) patients with doxycycline HCl, 500 mg, for an average duration of 8.9 months (range, 1 to 27 months). Twelve patients received intravenous morphine, 10 mg, before instillation of doxycycline. Chest pain was reported in 4 (22%) patients, and 2 of the 4 patients with chest pain had received morphine. Fever occurred in 4 (22%) patients during the first 24 hours after instillation.

Muir and associates [30] treated 27 patients who had malignant pleural effusions with doxycycline, 500 mg, through a chest tube; the tube was clamped for 24 hours. The procedure was repeated every 24 hours until tube drainage approximated the amount of fluid instilled; an average of 11 days was required. Complete response was reported in 22 (81%) patients. Two patients responded after a single dose of doxycycline, 1 patient after two doses, 4 (15%) patients after three doses, and 4 (15%) patients after four doses. Eight patients required 2.5 to 5.0 g of doxycycline, 6 patients required 6.0 to 9.5 g, and 2 patients required 10.5 g and 28 g. Even though larger doses of doxycycline were administered, adverse effects were similar to those in previously published studies on doxycycline. Pain occurred in 5 (19%) patients, fever in 10 (37%) patients, and an urticarial rash in 1 patient.

Minocycline

Intrapleural minocycline (Minocin, American Cyanamid), 300 mg with 1% lidocaine, was given to seven patients with malignant pleural effusions [33] (see Table 1). Six of the seven [86%] patients responded "completely" after a single dose of minocycline. However, the small number of patients, unspecified success rate criteria, and response duration make comparisons with other agents problematic. One patient reported pain. Serum minocycline concentrations were not measured and may be of concern because vestibular symptoms have occurred in 30% to 90% of patients at usual 200-mg intravenous daily doses [3, 34]. Vertigo, dizziness, ataxia, nausea, vomiting, and tinnitus have been reported in patients 1 to 3 days after receiving intravenous minocycline, 100 mg every 12 hours, with the symptoms resolving 48 hours after withdrawal of the drug. Symptoms appear to be related to the dose regimen and possibly to female sex. When receiving the same dose as men, women tend to have higher serum concentrations and are at a two to three times higher risk for developing vestibular toxicities than are men [35]. Studies with intrapleural minocycline and tetracycline in the rabbit pleural model suggest an inflammatory dose-response relation [36-40]. Extrapolating from experimental and human data on tetracycline, doses of minocycline, 300 mg or 4 to 5 mg/kg body weight, appear to be rational starting points.

Bleomycin

Intrapleural administration of bleomycin (Blenoxane, Bristol-Myers; Princeton, New Jersey), 1 unit/kg or 1 mg/kg [41] (15 to 240 units), produced a complete response in 108 (54%) of 199 patients with malignant pleural effusions [24, 29, 42-47] (Table 2). Pain, fever, and nausea were reported in 28%, 24%, and 11% of patients, respectively. Other adverse effects reported include hemoptysis [29], fluid accumulation and septic shock [29], rash [42], and diarrhea [45]. Forty-five percent of an intrapleural bleomycin dose is absorbed into the systemic circulation; however, alopecia and pulmonary fibrosis have rarely been reported [48]. The technique of intrapleural bleomycin administration is similar to that for tetracycline: The pleural effusion is drained by chest tube; bleomycin is instilled through the tube; and the chest tube is clamped for 2 to 6 hours and then reconnected to suction. The mechanism of action of bleomycin and the other cytotoxic antineoplastic agents is unknown. It may be caused by a combination of antineoplastic and fibrogenic effects and appears to operate differently than that of tetracycline [16].

Ruckdeshel and colleagues [29] conducted a multicenter, randomized trial comparing intrapleural bleomycin, 60 units (37 patients), with intrapleural tetracycline, 1 g (36 patients). Ninety days after the agents were instilled, 30% of the patients in the bleomycin group and 53% in the tetracycline group had recurrent effusions (P = 0.05). Reported adverse effects were similar in the groups: 36 percent with bleomycin and 37% with tetracycline. The major disadvantage of bleomycin is its cost, approximately $1104 for a 70-unit dose [49] (Table 3).

Cisplatin and Cytarabine

Markman and associates [50] first reported the use of intrapleural cisplatin (Platinol, Bristol-Myers) and cytarabine (Cytosar-U, Upjohn; Kalamazoo, Michigan) in seven patients with malignant pleural effusions (see Table 2). Fluid was removed from the pleural cavity by a percutaneous thoracentesis catheter. One liter of intravenous hydration was administered 1 to 2 hours before administration of intrapleural cisplatin and cytarabine. Sodium thiosulfate was given as an intravenous bolus of 4 g/m² body surface area and followed by 12 g/m² for a period of 6 hours beginning at the time of pleurodesis. Cisplatin, 100 mg/m², and cytarabine, 600 mg/m², were administered through the intrapleural catheter. Four hours after instillation, the chest cavity was drained as completely as possible and the catheter was removed. Patients with fluid reaccumulation received a second cycle of intrapleural therapy 21 days later. Six of seven [86%] patients had a greater than 75% reduction in effusion size and improvement in symptoms for a median of 4 months (range, 2 to 12 months).

Rusch and colleagues [51] conducted a prospective trial in 46 patients with malignant pleural effusions. Nine patients died of progressive disease during the first 3 weeks of the study and were not evaluated for response. The patients received hydration, diuretics, and antiemetic medications as if they were receiving systemic chemotherapy. Intrapleural cisplatin, 100 mg/m², and cytarabine, 1200 mg, were administered through a chest tube and left in the pleural space for 4 hours. The chest tube was then unclamped, allowed to drain for no more than 2 hours and then removed. Complete response was defined as the absence of pleural fluid reaccumulation that could not be drained by thoracentesis. Three weeks after intrapleural therapy, 6 (16%) patients had a complete response for a median duration of 9 months.

In these two studies, cisplatin and cytarabine produced a complete response in only 27% of the patients and caused many different adverse effects. Nausea and vomiting was reported in 76% of patients, pain in 66%, cardiopulmonary symptoms in 54%, bone marrow suppression in 52%, and renal toxicity in 34%.

Doxorubicin

The use of intrapleural doxorubicin (Adriamycin, Adria; Columbus, Ohio) in doses of 10 to 40 mg was reported to have produced a complete response in 12 (24%) of 55 patients [20, 52, 53] (see Table 2). Adverse effects included pain [29%], fever (15%), nausea and vomiting (29%), and anorexia (24%). Cardiomyopathy or bone marrow suppression was not reported, although nadir counts were not routinely measured.

Kefford and colleagues [20] conducted a trial comparing doxorubicin, 30 mg, in 11 patients with tetracycline, 500 mg, in 10 patients and nitrogen mustard, 20 mg, in 9 patients. Complete response was defined as the absence of pleural fluid on chest radiographs for 8 weeks. Two (18%) patients in the doxorubicin group responded; no patients in the nitrogen-mustard group responded completely. The 10% success rate in the tetracycline group may be attributed to the lower dose (500 mg) used. Reported adverse effects were similar among the three groups; however, the study included 11 peritoneal effusions and 1 pericardial effusion, and the authors did not separate the adverse effects according to type of effusion.

Etoposide

Holoye and associates [54] evaluated the use of intrapleural etoposide (VePesid, Bristol-Myers) in nine patients with malignant pleural effusions (see Table 2). After therapeutic thoracentesis, etoposide, 100 mg/m², was administered intrapleurally for 2 hours. The initial dose was repeated on days 8 and 15, and the cycle of three once-weekly infusions was repeated every 4 weeks until a response was seen. Success was defined as disappearance of the pleural effusion on a chest radiograph. A 50% dose escalation was allowed if only grade 0 to 1 toxicity [not defined] occurred and if the absolute granulocyte count was greater than 2000 mm³ and the platelet count was greater than 100 x 10⁹/L. Four patients received five cycles of 100 mg/m², five received 15 cycles of 150 mg/m², and three received three cycles of 225 mg/m². Serial chest radiographs showed no response in the nine evaluable patients. Reported adverse effects were progressive alopecia, emesis, and malaise. Myelosuppression was mild at doses of 150 mg/m²; more severe myelosuppression occurred at doses of 225 mg/m².

Fluorouracil

Fluorouracil (Adrucil, Adria) was administered intrapleurally in doses of 2 to 3 g in 35 patients with malignant pleural effusions [55] (see Table 2). Before instillation, most of the pleural fluid was removed by thoracentesis. Improvement was defined as no further reaccumulation of fluid on a chest radiograph or a decrease in the requirement for thoracentesis. Of the 35 patients treated, 23 [66%] improved. No patients reported pain, fever, stomatitis, or emesis; however, some patients reported nausea.

Interferon-ß

Natural interferon-ß (Frone; Serono, Italy) has been instilled intrapleurally in 29 patients with malignant pleural effusions [56] (see Table 2). Before pleurodesis, effusions were maximally aspirated by thoracentesis. Five million units of interferon-ß were injected through the thoracentesis needle, and the patients were instructed to move from side to side every 10 minutes for 1 hour. A complete response was defined as no further accumulation of fluid on chest radiograph within 30 days of pleurodesis. In cases of recurrence, therapy was repeated with successive 5 or 10 million units [range, 5 to 35 million units]. Diffuse pruritus, the only reported adverse effect, occurred in two patients.

Mitomycin-C

Luh and colleagues [57] evaluated the use of intrapleural mitomycin-C (Mutamycin, Bristol-Myers) in 27 patients with malignant pleural effusions (see Table 2). The patients had chest tube or pig-tail catheter drainage of the pleural effusion until the chest tube drainage was less than 200 mL/d. Mitomycin-C, 8 mg, was instilled into the pleural cavity and the chest tube was clamped for 1 hour. The instillation was repeated weekly for 4 weeks. If the effusion resolved before four doses were given, the treatment was discontinued, and the chest tube or catheter was removed. Complete response was defined as absence of fluid accumulation and symptoms for at least 4 weeks. Eleven [41%] patients had a complete response requiring an average of 2.8 injections of mitomycin-C. The median effusion-free period was 1.5 months. Reported adverse effects included fever (11%), pain (7%), dyspnea (7%), and leukopenia (4%).

After observations that systemic Corynebacterium parvum (Copravax, Wellcome Research; Beckenham, Kent, United Kingdom) had anticancer activity, the first use of intrapleural administration of C. parvum for pleurodesis surfaced during an open trial in six patients with malignant ascitic and pleural effusions [58]. Results of a subsequent study showed that C. parvum recruited neutrophils, and not mononuclear cells, into the pleural space, and the investigators concluded that C. parvum acts more as a fibrogenic agent than an immunostimulator with cellular-mediated properties [59].

Since 1978, C. parvum has been studied in nine series in Europe [22, 44, 47, 58-63] (see Table 1). Copravax, which contains 7 mg of dried, killed C. parvum, is available in Europe but not in the United States. Complete response has been documented in 129 of 169 [76%] patients. Reported adverse effects include fever (5%), pain (43%), cough (6%), and nausea (39%). There has been one case each of empyema and bronchopneumonia reported with intrapleural C. parvum [61].

Four of the nine studies compared C. parvum with other agents. Millar and associates [60] randomly assigned 21 patients, each with at least two recurrent malignant pleural effusions, to treatment with either 20 mg of nitrogen mustard compound, 20 mg of mustine, or 7 mg of Copravax. Patients were followed a mean of 79 days (range, 25 to 125 days), with 5 of 12 (42%) and 9 of 13 (69%) showing complete responses with mustine and C. parvum, respectively. All 12 patients given mustine had severe nausea and vomiting. Leahy and associates [22] compared 7 mg of Copravax with 500 mg of tetracycline in 32 patients in a randomized trial. No difference was seen in response rates of 82% and 69% with C. parvum and tetracycline, respectively. Hillerdal and colleagues [44] compared 60 mg of bleomycin with 7 mg of Copravax in a randomized study of 32 patients. An unusually low response rate of 2 of 15 (13%) patients was seen with bleomycin compared with 11 of 17 (65%) with C. parvum. The most comprehensive study by Ostrowski and colleagues [47] evaluated 58 patients in a randomized comparison of 60 mg of bleomycin and 7 mg of Copravax. Forty-four patients were alive at 30 days for assessment. Complete response was seen in 12 of 25 (48%) patients with bleomycin and 6 of 19 (32%) patients with C. parvum (P > 0.13). Differences approached significance in patients with breast carcinoma only; 9 of 19 (47%) and 3 of 14 (21%) responded to bleomycin and C. parvum, respectively (P = 0.06). Duration of response was followed to 1 year, and partial and complete responses were combined. There was a trend for longer response duration for bleomycin both at 6 months (bleomycin, 8 of 25, 32%; C. parvum, 3 of 19, 16%) and at 1 year (bleomycin, 4 of 25, 16%; C. parvum, 1 of 19, 5%). Fever was more common with C. parvum (53% compared with 24%, P = 0.02), with a trend for nausea to be more common with bleomycin (28% compared with 11%, P = 0.16). The authors suggest that the predominance of lung cancer effusions in earlier studies, when compared to their higher proportion of patients with breast cancer, might explain the lower efficacy seen in this study.

Methylprednisolone Acetate

Previously, long-acting corticosteroids have been used to treat pericardial effusions in patients with uremia [64, 65]. The precise mechanism of action of corticosteroids in malignant pleural effusions is unknown, but they appear to have a substantial local effect. It is thought that these agents act directly on tumor cells through various subsets of reticuloendothial cells present or by affecting the permeability of the visceral and parietal pleura [66].

Bartal and associates [66] studied the effects of intracavitary methylprednisolone acetate (Depo-Medrol, Upjohn) in 10 patients with recurrent malignant pleural effusions (see Table 1). Fluid was drained from the pleural cavity by thoracentesis; no attempt was made to remove the effusion completely. Following thoracentesis, methylprednisolone acetate, 80 mg, was injected into the pleural cavity. Thereafter, 160 mg was usually administered on a biweekly basis. Three [30%] patients had a complete response (not defined) and remained free of recurrent fluid for 11, 10, and 8 months, respectively. The patients received a median of three courses (range, 2 to 6 courses) of intrapleural therapy, and the total dosage averaged 420 mg (range, 160 to 820 mg). No adverse effects were reported.

Talc

Talc Insufflation

To assure uniform distribution, most clinicians have insufflated talc (Talc USP, Mallinckrodt, Paris, Kentucky) to the lung surface through a thoracoscope under general anesthesia, although instillation of talc as a slurry by tube thoracostomy under local anesthesia has been used [67, 68]. Talc is thought to cause pleural symphysis as a result of reactive pleuritis [69]. Because of the risk for developing malignant mesothelioma, asbestos-free, United States Pharmacopeia (USP) talc should be used for intrapleural administration [69-71].

Talc has been administrated to 165 patients with malignant pleural effusions [23, 68, 70-75] (see Table 1). A complete response was achieved in 153 [93%]. A review [76] on the administration of 5 to 10 g of talc by insufflation states that talc is more effective than tetracycline [23] and bleomycin [77]. In a randomized controlled trial, Fentiman and colleagues [23] compared the use of intrapleural tetracycline (n = 21) and intrapleural talc (n = 12) in patients with pleural effusions from breast cancer. Tetracycline, 500 mg, was instilled into the pleural cavity, and the drains were left in place 3 to 5 days. Talc was insufflated and intercostal drains were inserted and remained in place 5 days after pleurodesis. To be evaluable, patients had to survive for more than 1 month after pleurodesis. Success was defined as the continued absence of fluid on all follow-up chest radiographs for a minimum of 1 year. Ninety-two percent of the talc group and 48% of the tetracycline group were considered to have had successful therapy (P = 0.02). The lower success rate for tetracycline may be attributed to the lower dose (500 mg) used. Surgical emphysema occurred in two patients in the talc group and in 3 patients in the tetracycline group. In the talc group, 2 patients developed wound infections at the drain site, and 2 patients had asystolic arrest under general anesthesia; however, both patients were successfully resuscitated.

Aelony and associates [75] evaluated 42 patients treated with talc insufflation via a thoracoscope. Asbestos-free talc, 2.5 g USP (sterilized with ethylene oxide), was blown into the trocar using a rubber bellows and glass cylinder. Distribution of the talc was confirmed by direct visualization. At least 4 weeks of follow-up were required for radiographic and clinical evaluation. Chest radiographs were done at 1, 3, and 12 months; clinical success was defined as not requiring further thoracentesis for symptomatic relief of dyspnea. Twenty-three (82%) patients had permanent elimination of fluid confirmed by roentgenogram, and 28 (100%) patients had clinical success. Of the 5 patients who did not respond, 3 had a trapped lung that prevented complete elimination of fluid, and 2 patients had a mesothelioma. Two patients who previously had unsuccessful pleurodesis with 20 mg/kg of tetracycline had success with talc insufflation. No deaths were attributed to the procedure. Twenty-four patients were hospitalized for a mean of 3.9 days; the remaining patients were already hospitalized. Fever occurred in 54% of the patients. Other reported adverse effects were hemoptysis and cellulitis, each in one patient. There were no reports of severe pain; however, intravenous fentanyl was sometimes administered.

Talc Slurry

One unreported and two reported studies have investigated the use of talc in a liquid slurry formulation with instillation via chest tube. Sorensen and associates [74] used 10 g of talc in 250-mL 0.9% saline over 2 hours after chest tube drainage in 14 patients. After five patients were excluded due to lung failure in 72 hours, the remaining nine (100%) patients obtained complete response by chest radiograph until their deaths (median, 10 months; range, 3 to 24 months). Webb and associates [68] used 5 g of talc plus 3 g of thymol iodide (gas sterilized) and 20 mL of 1% lidocaine in 50-mL saline over 2 hours after chest tube drainage in 34 patients (three bilateral). Average time to removal of the chest tube was 4.6 days (range, 3 to 11 days). Complete response by radiograph at 1 month was seen in 34 (100%) patients. Mild temperature elevation was observed, and moderate pain was reported. A prospective evaluation of 52 patients treated with talc slurry, 10 g in 150- to 250-mL saline via chest tube showed a complete response in 35 (74%) of 47 evaluable patients (69 procedures) (Kennedy L, Rusch V. Unpublished data). Adverse effects consisted of fever (62%), empyema (6%), transient hypotension (4%), atrial arrhythmia (3%), and respiratory failure with ventilatory support in one patient.

Because patients generally require only one instillation of talc and no further thoracentesis, talc is thought to be one of the most effective sclerosing agents available to treat malignant pleural effusions [78]. However, the administration of talc usually requires thoracoscopy and is not without limitations. Rinaldo and colleagues [79] described three patients who developed the adult respiratory distress syndrome after receiving saline suspensions of large quantities (10 g) of talc through a chest tube. There have been reports of granulomatous pneumonitis [80], pulmonary edema [81], and brain microembolization [82] after talc instillation. Other disadvantages may include the need for physicians to have special training in thoracoscopy, the need for operating-room space, the need for general anesthesia, and the potential hazards from an induced pneumothorax. Talc has been administered, however, through a chest tube [67, 68, 74] or by thoracoscopy [83] under local anesthesia [68, 74, 75].

Costs of Agents

The charges for agents used for chemical pleurodesis vary from $0.50 for 10 g of talc USP to $1104 for 70 units of bleomycin (see Table 3). The charges for doxycycline range from $86 to $403, depending on the number of instillations required. A single 300-mg dose of minocycline costs $76. The charge for 2.5 to 10 g of talc USP is minimal, ranging from $0.15 to $0.50; however, charges for sterilization [69], thoracoscopy, general anesthesia, and the operating room substantially increase the cost to the patient.

Discussion

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Chemical pleurodesis is a universally accepted treatment for patients with recurrent, symptomatic, malignant pleural effusions, and various agents have been used to effect pleurodesis. Intrapleural tetracycline, which has been the agent of choice in the United States, is no longer available. American Cyanamid, the only manufacturer of intravenous and intramuscular tetracycline, has ceased production of these agents due to discontinuation of their market source of the sterile tetracycline salt [84]. Practicing clinicians must now select the best alternative for chemical pleurodesis. In addition, the re-emergence of thoracoscopy also necessitates the reassessment of the clinician's approach to malignant pleural effusions.

The current review has several limitations. Many trials studied small numbers of patients. Only four agents (tetracycline, bleomycin, C. parvum, and talc) were studied in more than 100 patients. Single and comparative studies are difficult to assess for effectiveness and toxicity because of differences in pleurodesis technique, variable success criteria, different lengths of follow-up, and the high rate of disease progression and death within the first month after pleurodesis. Not all agents have been compared comprehensively with one another under the same conditions and in the same patient population. Many studies did not provide specific information on the agent administered or objective outcome measurements. In some studies, patient samples included patients with pericardial and peritoneal effusions with or without pleural effusions. In others, adverse effects were causally addressed, making comparison problematic.

Doxycycline and minocycline appeared to be effective tetracycline-replacement agents in the small number of patients studied. However, some doxycycline-treated patients required multiple instillations for complete response. These results may be due to lower doses of doxycycline (7 mg/kg) than the previously used doses of tetracycline (20 mg/kg). Recent comparative studies with minocycline and tetracycline in rabbits suggest an inflammatory dose-response relation providing greater efficacy at higher minocycline doses (10 to 20 mg/kg) [39, 40]. The efficacy and safety of higher-dose minocycline and doxycycline has yet to be determined in humans. Except for bleomycin, the antineoplastic agents reviewed appear to cause more adverse effects with decreased efficacy compared with the tetracyclines, C. parvum, and talc. Although it has been more extensively studied, intrapleural bleomycin appears to be no more effective than minocycline and doxycycline and is substantially more expensive. Talc appears to be the most effective and least expensive agent but has the disadvantages of the need for and expense of thoracoscopy, the usual need for general anesthesia, and the potential hazards from an induced pneumothorax. However, a recent study used local anesthesia with intravenous sedation to insufflate talc by thoracoscopy in 25 patients with greater pleurodesis at 90 days (88%) compared with bleomycin (70%) or tetracycline (47%) in 88 historical control patients [83]. Further, talc usually requires only a single administration.

Recommendations

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What is the most practical approach today for the clinician treating a patient with a recurrent, symptomatic malignant pleural effusion? The answer is still controversial, and further studies are needed to determine the best cost-effective agent. Talc appears to be the most effective; however, when delivered by insufflation through a thoracoscope under general anesthesia, the expense escalates. Talc can be insufflated under local anesthesia or administered by slurry through a chest tube, which lowers the cost. However, appropriate doses and the adverse-effect profile have not been determined for the slurry, and only a limited number of patients have been studied. The availability of thoracoscopy in the clinician's community may limit the use of talc. The efficacy of bleomycin and the tetracycline-class agents minocycline and doxycycline are similar; however, the cost of bleomycin is substantially greater. Doxycycline or minocycline at doses of at least 500 mg and 300 mg, respectively, given through a chest tube appears to be a reasonable, cost-effective alternative.